Short-term effect of gluten-free diet on disease severity, quality of life, and inflammatory markers among patients with mild to moderate ulcerative colitis: A triple-blind randomized placebo-controlled trial.

BACKGROUND AND STUDY AIMS: Diet is an important underlying factor in ulcerative colitis (UC) disease. The present study aimed to investigate the effect of a gluten-free diet (GFD) on disease severity, quality of life, and inflammatory markers in patients with UC. PATIENTS AND METHODS: In this triple-blind randomized placebo-controlled clinical trial, we evaluated the effect of a GFD on the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, disease severity, and quality of life in patients with mild to moderate UC. Patients' quality of life and severity of symptoms were evaluated using the Inflammatory Bowel Disease Questionnaire (IBDQ) and Simple Clinical Colitis Activity Index (SCCAI), respectively. Patients received this regimen for six weeks and were evaluated before and after the intervention. RESULTS: The mean age of patients (n = 26) was 39.31 years (standard deviation = 9.34). In both study groups, the mean ESR, CRP, IBDQ, and SCCAI showed no statistically significant improvement with the dietary intervention. Fecal calprotectin was increased in both groups without statistical significance. CONCLUSIONS: We could not find any significant effect of GFD on inflammatory markers, quality of life, and disease severity among patients with mild to moderate UC. It is too early to suggest the gluten-free diet as a safe and beneficial regimen for UC patients. There is a need for further investigations with larger sample sizes and longer follow-ups as clinical trials and cohort studies to obtain more reliable results.

Association of Aberrant Promoter Methylation Changes in the Suppressor of Cytokine Signaling 3 (SOCS3) Gene with Susceptibility to Crohn's Disease.

Background: Growing evidence supports that changes in the methylation state of Inflammatory Bowel Disease (IBD)-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We supposed that alterations in DNA methylation status at promoter region within the suppressor of cytokine signaling 3 (SOCS3) gene in intestinal tissues may be involved in the susceptibility to Crohn's Disease (CD). Methods: DNA methylation status in the promoter region of the human SOCS3 gene of intestinal tissues from 15 patients with CD and 15 age- and sex-matched healthy controls were profiled using the real-time Quantitative Multiplex Methylation Specific PCR (QM-MSP) assay. Results: Based on methylation assay data profiling, we found that patients with CD showed a higher degree of methylation of the SOCS3 gene promoter region than did the healthy controls (unmethylated DNA in CD vs. healthy controls; 0.00048±0.0011 vs. 0.07±0.142, p<0.000). Conclusion: The data presented here demonstrate that aberrant methylation of the CpG islands within promoter regions of SOCS3 gene in colonic mucosa of CD was associated with mucosal inflammatory status, providing insights into the involvement of methylation could contribute to the initiation of the inflammatory process and development of CD.

Association between Promotor hypomethylation of TFF1 and Crohn's Disease.

BACKGROUND AND AIM: Epigenetic modifications exhibit promising evidence in etiology and prognosis of important diseases such as inflammatory bowel diseases (IBD). In addition to complex factors involved in IBD, a trend toward better prognosis have been reported in older ages of disease onset. Gastrointestinal mucous layer is one of the important components which is disturbed in the disease course. Integrity of this layer is maintained with an anti-inflammatory factor called trefoil factors (TFF). We investigated the methylation status of TFF1 gene in IBD patients alongside with correlation of its alteration level with age of disease onset. METHODS: We analyzed the promoter methylation status of TFF1 gene, using the real-time quantitative multiplex methylation specific PCR (QM-MSP). DNA was extracted from colorectal biopsies of 15 Crohn disease cases and 15 healthy controls. Correlation analysis was performed between unmethylated DNA level and age through Pearson correlation coefficient (PPC) test and simple linear regression models. RESULTS: … Our data didn't provide significant positive correlation of age and TFF1 hypomethylation in Crohn patients (r = .518, p = .058). CONCLUSIONS: In conclusion, our case-control study didn't show significant alteration in TFF1 methylation status in CD patients. (www.actabiomedica.it).

Irritable Bowel Syndrome Demographics: A Middle Eastern Multinational Cross-sectional Study.

BACKGROUND: Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal (GI) disorder. In this study, we aimed to evaluate the different aspects of IBS among Middle Eastern residents. METHODS: During the study period, patients attending gastroenterology clinics of nine tertiary referral centers in four Middle Eastern couturiers (Iran, Egypt, Kuwait, and Turkey) were evaluated by Rome IV diagnostic criteria, and those who fulfilled the diagnostic criteria of IBS were asked to fill in a questionnaire covering different demographics and clinical aspects. RESULTS: Overall, during a 6-month period, 509 patients with IBS were included. 41.3% of the participants were male (210 patients), and 37.4% of them had academic education. 50% of the participants were Caucasian, and 34% were Arab, and originally, they were citizens of 18 countries. 77.4% of the participants were residents of subtropical areas, while 22.2% were living in temperate regions. The average age of the participants during the first presentation in subtropical and temperate areas were 38.4 ± 12.19 and 38.06 ± 12.18 years, respectively (P = 0.726). The most common subtypes of IBS in subtropical areas were unclassified (IBS-U, 44.4%), constipation dominant (IBS-C, 27.6%), mixed pattern (IBS-M, 21%), and diarrhea dominant (IBS-D, 6.8%) in descending order while in temperate areas the most common subtypes were IBS-U (43.3%), and IBS-D (22.1%), respectively (P < 0.001). Besides abdominal pain, the most common symptom of patients in each region was bloating (62.2% and 68.1%, respectively, P = 0.246). The rate of depression and anxiety were significantly higher among the residents of temperate areas in comparison with subtropical regions (41.6% vs. 16.5% and 80.5% vs. 58.4%, respectively, P < 0.001). CONCLUSION: Although the average age of IBS presentation is the same in subtropical and temperate areas, it seems that in temperate areas, the rate of IBS-D is more prevalent than in subtropical regions. The rate of anxiety and depression are significantly higher among those who searched social media and the internet to get information about their problems.

Vortioxetine effects on quality of life of irritable bowel syndrome patients: A randomized, double-blind, placebo-controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease causing a substantial productivity loss with no definite treatment. Our study investigates the effects of vortioxetine vs placebo in enhancing the IBS patients' quality of life. METHODS: In a double-blinded, placebo-controlled, randomized trial, adults with IBS, according to the ROME IV criteria, were randomized to placebo and vortioxetine for 6 weeks. Participants were visited every two weeks to fill IBS quality of life, hospital anxiety and depression scale, and adverse effect questionnaires. RESULTS: Eighty patients were randomized, and seventy-two finished the trial. Baseline characteristics of groups were similar. Both placebo and vortioxetine significantly increased the quality of life during course of the study (both P-values < .001), whereas vortioxetine demonstrated a greater increase (P-value < .001). According to the analysis of covariances, this enhancement was irrespective of depression or anxiety score changes (P-value = .002). Adverse effect profile was similar between the groups and can increase IBS patients' quality of life superior to placebo. Vortioxetine effects in our study were observed irrespective of the depression and anxiety levels.

Clinical and Pathological Features of Ulcerative Colitis in Patients with and without Clostridium Difficile Infection; An Observational Study.

BACKGROUND A dramatic rise in the rate of clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD) has been reported in recent years. METHODS In this observational case control study, 65 patients were included and were divided into two groups of IBD + CDI as case group and IBD without CDI as control group. RESULTS 35 patients who had positive test for clostridium difficile were assigned to the case group. The control group consisted of 30 patients with negative test for clostridium difficile. Pancolitis was seen in the cases more statistically significant than the controls and proctitis was seen more among the controls than the cases (p = 0.001). The cases were on immunosuppressive (p = 0.001) and antibiotic (p = 0.02) therapy more than the controls. Colonoscopic findings revealed more severe and extensive inflammation among the cases versus milder inflammation among the controls, but these differences were not statistically significant (p = 0.2). Colectomy was seen in 10% of controls and none of the cases and this difference was statistically significant (p value = 0.05). More fecal calprotectin were seen among the cases than the controls and this difference was statistically significant (p < 0.05) CONCLUSION This study showed more clostridium difficile infection among the patients on antibiotic or immunosuppressive therapy. Pathological investigation revealed more severe and extensive inflammation among the cases than the controls. Cases had clinically more severe signs and symptoms with higher mayo scores than the controls. ESR (Erythrocyte sedimentation rate) and fecal calprotectin were higher in patients with positive clostridium difficile infection and serum albumin was lower in such patients.

Dysbiosis of fecal microbiota and high frequency of Citrobacter, Klebsiella spp., and Actinomycetes in patients with irritable bowel syndrome and gastroenteritis.

AIM: This study was aimed to characterize putative differences of fecal microbiota between irritable bowel syndrome (IBS) and gastroenteritis patients and healthy controls. BACKGROUND: New evidence proposed that gut microbiota has a deep effect on the balance between health and disease. PATIENTS AND METHODS: The presence of Clostridium difficile, Campylobacter spp., Enterobacteriacea and Staphylococci were detected in the samples using selective and specific culture media. Microscopic examination of the samples was done to detect Actinomycetes, yeasts, Bifidobacteria, Fusobacterium spp., as well as white blood cells, red blood cells, mucus and epithelial cells. RESULTS: Results of this study showed relatively higher frequency of Citrobacter spp., Lactobacilli, and Actinomycetes in the IBS patients. Elevated levels of WBC, RBC secretion, and increased amounts of Klebsiella, Escherichia coli and Citrobacter spp. were characterized in the patients with gastroenteritis compared with the control group. CONCLUSION: Depletion of gram positive cocci and gram negative bacilli also suggested dysbiosis of intestinal microbiota in these patients.

Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open labeled, controlled study.

A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Participants were assigned to take either a lifestyle modification (LM), or LM +30 g/day brown milled flaxseed for 12 weeks. At the end of the study, body weight, liver enzymes, insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups (p< 0.05); however, this reduction was significantly greater in those who took flaxseed supplementation (p < 0.05). The significant mean differences were reached in hepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; P< 0.001], AST [-8.29 compared with -4 U/L; p < 0.001], GGT [-15.7 compared with -2.62 U/L; p < 0.001], fibrosis score [-1.26 compared with -0.77 kPa; p = 0.013] and steatosis score [-47 compared with -15.45 dB/m; p = 0.022]. In conclusion, flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management.

A review of the clinical manifestations, pathophysiology and management of opioid bowel dysfunction and narcotic bowel syndrome.

Opioids are widely used for the treatment of malignant and non-malignant pains. These medications are accompanied by adverse effects, in particular gastrointestinal symptoms known as opioid bowel dysfunction (OBD). The most common symptom of OBD is refractory constipation that is usually stable regardless of the use of laxatives. Narcotic bowel syndrome (NBS) is a subset of OBD described as ambiguous chronic pain aggravated by continual or increased opioid use for pain relief. Pathophysiology of these disorders are not definitely disentangled. Some challenging hypothesis have been posed leading to specific management in order to mitigate the adverse effects. This article is a review of the literature on the prevalence, pathophysiology and management of OBD and NBS.

Comparison of five diagnostic methods for Helicobacter pylori.

BACKGROUND AND OBJECTIVES: Invasive and non-invasive techniques are used to diagnose H. pylori infection. Some factors influence the choice of a diagnostic test, such as the sensitivity and specificity of the tests, the clinical circumstances and the cost-effectiveness of the testing strategy. The aim of this study was to reveal the relationship between different H. pylori infection diagnosis methods, and clarify the application scope of each diagnosis method. MATERIALS AND METHODS: patients were included in the study, and specimens including biopsies, blood and stool were taken. Biopsies were evaluated by hematoxylin and eosin, and Giemsa staining. A sequence of 294 bp in the ureC (glmM) gene was amplified. The rapid urease test (RUT) was performed using a non-commercial validated test. Stool samples were analyzed using a polyclonal ELISA stool antigen test. A serological assay for IgG antibodies was performed by a commercial Helicobacter pylori IgG ELISA kit. RESULTS: According to the predefined criteria, a total of 46 (50.5%) patients tested were positive by at least 2 of the 3 biopsy-based methods. The best sensitivity (95.6%) belonged to histology and RUT. The sensitivities of other tests including PCR, serology and stool antigen test were 93.5%, 91.3% and 73.9%, respectively. RUT showed the best specificity (100%), and the specificities of the other tests, including PCR, stool antigen test, histology and serology, were 95.6%, 86.7%, 77.8% and 55.6%, respectively. CONCLUSION: In view of the better results obtained for invasive vs non-invasive tests, for a more accurate diagnosis, it is advisable not to solely rely on non-invasive methods of H. Pylori diagnosis.

Evaluation of health related quality of life in irritable bowel syndrome patients.

BACKGROUND: Quality of life (QOL) is an important measure in the management of Irritable Bowel Syndrome (IBS). Controversy exists in the findings of studies evaluating QOL in IBS subtypes, and little is known about this issue in Iranian patients. Determination of the factors affecting QOL in IBS patients may influence treatment outcomes. The aims of this study are to: 1) compare QOL between subtypes in a sample of Iranian IBS patients, 2) determine the factors associated with QOL in IBS. METHODS: This cross sectional study included two hundred and fifty IBS patients with the mean age (± standard deviation) of 31.62 (± 11.93) years that were referred to outpatient gastroenterology clinic. IBS patients were diagnosed based on Rome-3 criteria by a gastroenterologist, and then they were categorized into three subtypes according to the predominant type of bowel habit. The "QOL specific for IBS", "Stait-trait anxiety inventory", and "Beck depression inventory-2" questioners were used to evaluate QOL, anxiety, and depression symptoms, respectively. RESULTS: The mean QOL scores in IBS mixed subtype (71.7 ± 25.57), constipation predominant subtype (80.28 ± 25.57), and diarrhea predominant subtype (76.43 ± 19.13) were not different. (P value: 0.05) In multivariate linear regression analysis, anxiety symptom scores were inversely correlated with QOL scores. [Standardized beta: -0.43, (95% confidence interval: -0.70, -0.39), P value: < 0.01] CONCLUSION: It seems reasonable to manage anxiety symptoms properly in IBS patients since this might increase their QOL.

Lack of Association between Interleukin 12 C(-1188)A Polymorphism and Irritable Bowel Syndrome.

Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. This study was performed to investigate the important role of interleukin-12 (IL-12) in intestinal inflammation. For this study seventy one patients with IBS and 140 controls were investigated. The allele and genotype frequencies of IL-12 C(-1188)A were determined using polymerase chain reaction with sequence-specific primers. The allele A was more common that the allele C in both groups of patients and controls. There was not any significant difference on IL-12 alleles and genotypes between patients and controls. The AA genotype was the most common genotypes, which was seen in 57.4% of the patients and 51.4% of the controls (p = 0.53). Although frequency of the CC genotype in the control group was lower than the patient group, this difference was not significant (5.7% vs. 11.5%, respectively, p = 0.16). Considering the lack of association between IL-12 C(-1188)A polymorphism and IBS, this cytokine gene polymorphism may not have significant role in the pathophysiology of disease.

Cutaneous granulomas in common variable immunodeficiency: case report and review of literature.

Common variable immunodeficiency (CVID) is a heterogeneous disease characterized by recurrent infections, autoimmunity, malignancies, and granulomatous inflammation. Granulomatous lesion is one of the important manifestations of CVID, which continues to be unknown to many clinicians. While noncaseating granulomatous lesions can be detected in lungs, liver, spleen or conjunctiva of CVID patients, there are only few reported cases with skin granuloma. This report presents a 27-year-old female with multiple persistent cutaneous granulomatous lesions on both hands. The patient had been well until age of 20 years, when she developed these skin lesions and frequent upper respiratory infections and bacterial pneumonia. Also, she experienced recurrent diarrhea (more than 10 episodes). Laboratory evaluation showed decreased serum levels of all immunoglobulin isotypes and low specific antibody responses. The diagnosis of CVID was based on clinical and laboratory findings. Intravenous immunoglobulin therapy at a dosage of 400-500 mg/kg monthly was introduced and improved skin lesions. In conclusion, taking history of recurrent infections and measuring immunoglobulin levels can be suggested in patients with granulomatous lesions instead of other expensive tests.

T-helper 1, T-helper 2, and T-regulatory cytokines gene polymorphisms in irritable bowel syndrome.

Inflammation and mucosal immune system activation have an important role in irritable bowel syndrome (IBS), whereas genetic factors can control some immunological mediators. In this study, a number of polymorphic genes coding for T-helper 1, T-helper 2, and T-regulatory cytokines were genotyped in 71 patients with IBS, and the results were compared with controls. IL-4 CC genotype at position -590, IL-4 TT genotype at position -33, and IL-10 GA genotype at position -1082 were significantly overrepresented in the patients with IBS in comparison with controls (P < 0.001). The frequencies of the following haplotypes in the patient group were significantly higher than in the control group: IL-2 (-330, +160) GT haplotype (P = 0.002), IL-4 (-1098, -590, -33) TCC haplotype (P < 0.001), and TCT haplotype (P < 0.001). While production of cytokines could be affected by genetic polymorphisms within coding and promoter regions of cytokine genes, IL-4 and IL-10 gene polymorphisms could affect individual susceptibility to IBS.

Proinflammatory cytokine gene polymorphisms in irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS) is a multifactorial functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. Proinflammatory cytokines can play an important role in intestinal inflammation, while their production is under genetic control. METHODS: This study was performed in a group of patients with IBS to analyze the genotype frequencies of a number polymorphic genes coding for proinflammatory cytokine (interleukin-6 (IL), tumor necrosis factor-alpha (TNF-alpha), and IL-1 group). Using polymerase chain reaction with sequence-specific primers method, the cytokine genes were amplified, and alleles and genotypes of 71 patients with IBS were detected on gel electrophoresis, and the results were compared with healthy control subjects. RESULTS: Results of the analyzed data showed that the frequencies IL-1R C allele at position Pst-I 1970 (P = 0.017), IL-6 G allele at position -174 (P = 0.002), and TNF-alpha G allele at position -238 (P < 0.001) in the patient group were significantly higher than the control group. IL-6 GG genotype (-174) and TNF-alpha GG genotype (-238) in the patient group were also significantly overrepresented (P < 0.001), while IL-6 CG genotype (-174) and TNF-alpha GA genotype (-238) were significantly decreased in the patients with IBS (P < 0.001). The frequencies of IL-6 (-174, nt565) GG haplotype and TNF-alpha (-308, -238) GG haplotype were also significantly higher in the patient group (P < 0.001), whereas the frequencies of the haplotypes IL-6 CG and TNF-alpha GA were significantly decreased in the patients with IBS (P < 0.001). CONCLUSION: IL-6 and TNF-alpha proinflammatory cytokine gene polymorphisms could change individual susceptibility to IBS and might have a role in pathophysiology of disease.