Solid Organ Transplantation in Patients with Inflammatory Bowel Diseases (IBD): Analysis of Transplantation Outcome and IBD Activity in a Large Single Center Cohort

Background

Currently, limited data of the outcome of inflammatory bowel disease (IBD) in patients after solid organ transplantation (SOT) are available. We aimed to analyze effects of SOT on the IBD course in a large IBD patient cohort.

Methods

Clinical data from 1537 IBD patients were analyzed for patients who underwent SOT (n = 31) between July 2002 and May 2014. Sub-analyses included SOT outcome parameters, IBD activity before and after SOT, and efficacy of IBD treatment.

Results

4.74% of patients with ulcerative colitis (UC) and 0.84% of patients with Crohn’s disease (CD) underwent SOT (p = 2.69 x 10⁻⁶, UC vs. CD). 77.4% of patients with SOT underwent liver transplantation (LTx) with tacrolimus-based immunosuppressive therapy after SOT. All LTx were due to primary sclerosing cholangitis (PSC) or PSC overlap syndromes. Six patients (19.4%) required renal transplantation and one patient (3.2%) heart transplantation. A survival rate of 83.9% after a median follow-up period of 103 months was observed. Before SOT, 65.0% of patients were in clinical remission and 5 patients received immunosuppressive therapy (16.1%). After SOT, 61.0% of patients were in remission (p = 1.00 vs. before SOT) and 29.0% required IBD-specific immunosuppressive or anti-TNF therapy (p = 0.54 vs. before SOT). 42.9% of patients with worsening of IBD after SOT were at higher risk of needing steroid therapy for increased IBD activity (p = 0.03; relative risk (RR): 10.29; 95% CI 1.26–84.06). Four patients (13.0%) needed anti-TNF therapy after SOT (response rate 75%).

Conclusions

SOT was more common in UC patients due to the higher prevalence of PSC-related liver cirrhosis in UC. Despite mainly tacrolimus-based immunosuppressive regimens, outcome of SOT and IBD was excellent in this cohort. In this SOT cohort, concomitant immunosuppressive therapy due to IBD was well tolerated.     

Associations between chronotype,sleep disturbances and seasonality with fatigue and inflammatory bowel disease symptoms

Growing number of studies suggests link between circadian rhythms and inflammatory bowel diseases (IBD) manifestation. We hypothesize that: 1) IBD are associated with increased eveningness and sleep disturbances; 2) eveningness and sleep disturbances are related to more severe IBD symptoms. In total, 129 participants were enrolled to this study, divided into three groups: 34 Crohn’s disease (CD) patients, 38 ulcerative colitis (UC) patients and 57 healthy controls (HC) group. They all fulfilled a questionnaire, consisting of the Composite Scale of Morningness (CSM), Seasonal Pattern Assessment Questionnaire (SPAQ), Pittsburgh Sleep Quality Index, Inflammatory Bowel Disease Questionnaire (IBDQ) and Multidimensional Fatigue Inventory (MFI). Multiple regression models controlled for age and sex revealed that in CD group higher eveningness measured with CSM was associated with higher general fatigue, physical fatigue, mental fatigue and reduced motivation measured by MFI. Lower CSM morning affect is associated with greater general fatigue, physical fatigue and more reduced activity. Greater seasonality scores are associated with increased physical fatigue and more reduced activity and motivation. Lower sleep quality measured with PSQI is associated with higher physical fatigue and more reduced activity. Correlational analysis revealed that higher seasonality and lower sleep quality are associated with increased systemic and bowel symptoms and decreased emotional and social functions measured with IBDQ. In UC group, eveningness is associated with greater general fatigue, physical fatigue and more reduced activity. Higher CSM morning affect is associated with decreased general fatigue, physical fatigue and less reduced activity. Higher CSM circadian preference scores are associated with decreased general and physical fatigue, and less reduced activity. Increased seasonality is associated with more physical fatigue. Lower sleep quality is associated with greater general and physical fatigue. To our best knowledge this is the first study evaluating associations between chronotype and sleep disturbances with IBD symptoms. We have found that chronotype preferences, whose role in IBD has been until now overlooked, may be one of the important factors contributing to fatigue in this clinical group.     

The insulin-like growth factor system and markers of inflammation in adult patients with inflammatory bowel disease

BACKGROUND AND OBJECTIVES: Catabolism and growth impairment are well-known complications of inflammatory bowel disease (IBD). Recent studies have demonstrated significant changes in the IGF system in IBD patients. The aim of the present study was to investigate correlations between the IGF system and markers of inflammation in IBD. METHODS: A cross-sectional study comprising 99 IBD patients (Crohn's disease (CD, n = 50) and ulcerative colitis (UC, n = 49)). Correlations between markers of inflammation and IGF-I, IGF-II and IGFBP-3 were examined in CD and UC patients in remission and relapse. The patients were clinically scored using Crohn's Disease Activity Index (CDAI) for CD patients and Activity Index (AI) for UC patients. RESULTS: In the UC group we found correlations between IGF-I and CRP (r(s) = Spearman's rho) (r(s) = -0.40, p < 0.01) and albumin (r(s) = 0.46, p < 0.001), IGFBP-3 and albumin (r(s) = 0.36, p < 0.01) and AI score (r(s) = -0.31, p < 0.05). IGF-II correlated with CRP (r(s) = -0.42, p < 0.01), IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01), AI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). In the CD group we found correlations between IGF-I and CRP (r(s) = -0.40, p < 0.05), and albumin (r(s) = -0.46, p < 0.01), IGFBP-3 and albumin (r = 0.36, p < 0.01). IGF-II correlated with IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01), CDAI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). CONCLUSIONS: IGF-I, IGF-II and IGFBP-3 are correlated to albumin and IGF-I and IGF-II are correlated to CRP in IBD patients. Further, IGF-II is correlated to IL-6 in IBD patients. This may suggest a correlation between inflammation and the IGF system with involvement in muscle and bone catabolism in IBD.     

Chaga mushroom extract inhibits oxidative DNA damage in lymphocytes of patients with inflammatory bowel disease

Inflammatory Bowel Disease (IBD) is partly caused by oxidative stress from free radicals and reduced antioxidant levels. Using hydrogen peroxide to induce oxidative stress in vitro in peripheral lymphocytes we investigated the induction of DNA damage supplemented with ethanolic extract of Chaga mushroom as a protective antioxidant. Lymphocytes were obtained from 20 IBD patients and 20 healthy volunteers. For treatment, a constant H_{2}O_{2 } dose (50 microg/ml) was used with variable doses of Chaga extract (10-500 microg/ml). DNA damage was evaluated in 50 cells per individual and dose using the Comet assay (making 1000 observations per experimental point ensuring appropriate statistical power). Chaga supplementation resulted in a 54.9% (p < 0.001) reduction of H_{2}O_{2 } induced DNA damage within the patient group and 34.9% (p < 0.001) within the control group. Lymphocytes from Crohn's disease (CD) patients had a greater basic DNA damage than Ulcerative Colitis (UC) patients (p < 0.001). Conclusively, Chaga extract reduces oxidative stress in lymphocytes from IBD patients and also healthy individuals when challenged in vitro. Thus, Chaga extract could be a possible and valuable supplement to inhibit oxidative stress in general.     

Genetic analysis of innate immunity in Crohn's disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP

The two main phenotypes of inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--are chronic intestinal inflammatory disorders with a complex genetic background. Using a three-stage design, we performed a functional candidate-gene analysis of innate immune pathway in IBD. In phase I, we typed 354 SNPs from 85 innate immunity genes in 520 Dutch IBD patients (284 CD, 236 UC) and 808 controls. In phase II, ten autosomal SNPs showing association at p < 0.006 in phase I were replicated in a second cohort of 545 IBD patients (326 CD, 219 UC) and 360 controls. In phase III, four SNPs with p < 0.01 in the combined phase I and phase II analysis were genotyped in an additional 786 IBD samples (452 CD, 334 UC) and 768 independent controls. Joint analysis of 1851 IBD patients (1062 CD, 789 UC) and 1936 controls demonstrated strong association to the IL18RAP rs917997 SNP for both CD and UC (p(IBD) 1.9 x 10(-8); OR 1.35). Association in CD is independently supported by the Crohn's disease dataset of the Wellcome Trust Case Control Consortium (imputed SNP rs917997, p = 9.19 x 10(-4)). In addition, an association of the CARD9 rs10870077 SNP to CD and UC was observed (p(IBD) = 3.25 x 10(-5); OR 1.21). Both genes are located in extended haplotype blocks on 2q11-2q12 and 9q34.3, respectively. Our results indicate two IBD loci and further support the importance of the innate immune system in the predisposition to both CD and UC.     

Identification of Restricted Subsets of Mature microRNA Abnormally Expressed in Inactive Colonic Mucosa of Patients with Inflammatory Bowel Disease

Background

Ulcerative Colitis (UC) and Crohn''s Disease (CD) are two chronic Inflammatory Bowel Diseases (IBD) affecting the intestinal mucosa. Current understanding of IBD pathogenesis points out the interplay of genetic events and environmental cues in the dysregulated immune response. We hypothesized that dysregulated microRNA (miRNA) expression may contribute to IBD pathogenesis. miRNAs are small, non-coding RNAs which prevent protein synthesis through translational suppression or mRNAs degradation, and regulate several physiological processes.

Methodology/Findings

Expression of mature miRNAs was studied by Q-PCR in inactive colonic mucosa of patients with UC (8), CD (8) and expressed relative to that observed in healthy controls (10). Only miRNAs with highly altered expression (>5 or <0.2 -fold relative to control) were considered when Q-PCR data were analyzed. Two subsets of 14 (UC) and 23 (CD) miRNAs with highly altered expression (5.2->100 -fold and 0.05–0.19 -fold for over- and under- expression, respectively; 0.001<p≤0.05) were identified in quiescent colonic mucosa, 8 being commonly dysregulated in non-inflamed UC and CD (mir-26a,-29a,-29b,-30c,-126*,-127-3p,-196a,-324-3p). Several miRNA genes with dysregulated expression co-localize with acknowledged IBD-susceptibility loci while others, (eg. clustered on 14q32.31), map on chromosomal regions not previously recognized as IBD-susceptibility loci. In addition, in silico clustering analysis identified 5 miRNAs (mir-26a,-29b,-126*,-127-3p,-324-3p) that share coordinated dysregulation of expression both in quiescent and in inflamed colonic mucosa of IBD patients. Six miRNAs displayed significantly distinct alteration of expression in non-inflamed colonic biopsies of UC and CD patients (mir-196b,-199a-3p,-199b-5p,-320a,-150,-223).

Conclusions/Significance

Our study supports miRNAs as crucial players in the onset and/or relapse of inflammation from quiescent mucosal tissues in IBD patients. It allows speculating a role for miRNAs as contributors to IBD susceptibility and suggests that some of the miRNA with altered expression in the quiescent mucosa of IBD patients may define miRNA signatures for UC and CD and help develop new diagnostic biomarkers.     

Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes

The contribution of rare coding sequence variants to genetic susceptibility in complex disorders is an important but unresolved question. Most studies thus far have investigated a limited number of genes from regions which contain common disease associated variants. Here we investigate this in inflammatory bowel disease by sequencing the exons and proximal promoters of 531 genes selected from both genome-wide association studies and pathway analysis in pooled DNA panels from 474 cases of Crohn’s disease and 480 controls. 80 variants with evidence of association in the sequencing experiment or with potential functional significance were selected for follow up genotyping in 6,507 IBD cases and 3,064 population controls. The top 5 disease associated variants were genotyped in an extension panel of 3,662 IBD cases and 3,639 controls, and tested for association in a combined analysis of 10,147 IBD cases and 7,008 controls. A rare coding variant p.G454C in the BTNL2 gene within the major histocompatibility complex was significantly associated with increased risk for IBD (p = 9.65x10⁻¹⁰, OR = 2.3[95% CI = 1.75–3.04]), but was independent of the known common associated CD and UC variants at this locus. Rare (<1%) and low frequency (1–5%) variants in 3 additional genes showed suggestive association (p<0.005) with either an increased risk (ARIH2 c.338-6C>T) or decreased risk (IL12B p.V298F, and NICN p.H191R) of IBD. These results provide additional insights into the involvement of the inhibition of T cell activation in the development of both sub-phenotypes of inflammatory bowel disease. We suggest that although rare coding variants may make a modest overall contribution to complex disease susceptibility, they can inform our understanding of the molecular pathways that contribute to pathogenesis.     

Risk of Ischaemic Heart Disease in Patients with Inflammatory Bowel Disease: Cohort Study Using the General Practice Research Database

ObjectivePatients with inflammatory bowel disease (IBD) demonstrate an inflammatory response which bears some similarities to that seen in ischaemic heart disease (IHD). The nature of the association of IBD with IHD is uncertain. We aimed to define the extent and direction of that association.DesignThis retrospective cohort study examined records from patients aged ≥ 15 years with IBD from 1987–2009 (n = 19163) who were age and gender matched with patients without IBD (n = 75735) using the General Practice Research Database. The primary outcome was the hazard ratio for IHD.ResultsA higher proportion of IBD patients had a recorded diagnosis of IHD ever, 2220 (11.6%) compared with 6504 (8.6%) of controls. However, the majority (4494, 51.5%) developed IHD prior to IBD diagnosis (1404 (63.2%) of IBD cases and 3090 (47.5%) of controls). There was increased IHD incidence in the first year after IBD diagnosis. Mean age at IHD diagnosis was statistically similar across all IBD groups apart from for those with Ulcerative Colitis (UC) who were slightly younger at diagnosis of angina compared to controls (64.5y vs. 67.0y, p = 0.008) and coronary heart disease (65.7y vs.67.9y, p = 0.015). Of those developing IHD following IBD diagnosis, UC patients were at higher risk of IHD (unadjusted HR 1.3 (95% CI 1.1–1.5), p<0.001) or MI (unadjusted HR 1.4 (95% CI 1.1–1.6), p = 0.004).ConclusionAlthough IHD prevalence was higher in IBD patients, most IHD diagnoses predated the diagnosis of IBD. This implies a more complex relationship than previously proposed between the inflammatory responses associated with IHD and IBD, and alternative models should be considered.     

Relationships between serum IGF-1, IGFBP-2, interleukin-1beta and interleukin-6 in inflammatory bowel disease

AIMS: To study the relationships between serum IGF-1, IGFBP-3 and IGFBP-2 and interleukin (IL)-1beta and IL-6 in inflammatory bowel disease (IBD). METHODS: Thirty-seven patients (18 males, 19 females, aged 8.8-26.1 years) with IBD (Crohn's disease, CD, n = 17, and ulcerative colitis, UC, n = 20) were studied. Patients were in relapse or remission according to established criteria. Serum IGF-1, IGFBP-3, IGFBP-2, IL-1beta and IL-6 levels were determined in patients and 15 healthy controls (aged 8.2-19.0 years). RESULTS: IGF-1 levels were lower in patients with CD in relapse compared with controls (p < 0.05). IGFBP-2 levels were higher in CD in relapse compared with other groups (all p < 0.05). In CD and UC patients (n = 37), IGF-1 levels were inversely correlated with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). IGFBP-2 levels correlated positively with ESR and IL-1beta. IL-6 levels correlated positively with ESR and CRP. IL-1beta levels were elevated in CD in relapse compared to controls (p < 0.05) and were higher in UC in relapse than in other groups (all p < 0.05). In combined CD/UC patients in relapse (n = 20), IL-1beta levels were higher (p < 0.05) in patients with recto-sigmoiditis (n = 5) than in other patients. CONCLUSIONS: IGF-1, IGFBP-2 levels were related to IL levels, disease activity and anatomical distribution, consistent with active inflammation modifying the IGF-IGFBP system, possibly relevant to disturbance of growth.     

Interleukin 35 (IL-35) and IL-37: Intestinal and peripheral expression by T and B regulatory cells in patients with Inflammatory Bowel Disease

The aim of the study was to characterize and to quantify peripheral and tissue. IL-35— and IL-37—producing cells in Inflammatory Bowel Disease (IBD) patients. We studied a total of 38 active UC, 31 inactive UC, 17 active CD, and 13 inactive CD and 50 non-inflamed tissues as control group. Gene expression was measured by real time polymerase chain reaction (RT-PCR) and protein expression was evaluated in tissue by immunohistochemistry and in peripheral blood mononuclear cells by flow cytometry. Higher levels of IL-35 was produced by intestinal regulatory B cells and circulating regulatory CD4⁺ and CD8⁺ T cells in active vs. inactive disease or healthy donors (P < 0.05). The IL-37 was conspicuously synthesized by circulating B cells, active natural killer cells and monocytes. These results suggest that down-regulation of inflammation in active IBD patients might be based on the increased expression of IL-35 and IL-37.     

Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort

Background

The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17 and the interferon gamma (IFNG) pathways are associated with risk of both CD and UC.

Methods

Using a candidate gene approach, 21 functional single nucleotide polymorphisms (SNPs) in 15 genes were assessed in a clinical homogeneous group of severely diseased ethnic Danish patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression.

Results

The polymorphisms TLR5 (rs5744174) and IL12B (rs6887695) were associated with risk of CD, and TLR1 (rs4833095) and IL18 (rs187238) were associated with risk of both CD and UC (p<0.05). After Bonferroni correction for multiple testing, the homozygous variant genotype of TLR1 743 T>C (rs4833095) was associated with increased risk CD (OR: 3.15, 95% CI: 1.59–6.26, p = 0.02) and CD and UC combined (OR: 2.96, 95% CI: 1.64–5.32, p = 0.005).

Conclusion

Our results suggest that genetically determined high activity of TLR1 and TLR5 was associated with increased risk of both CD and UC and CD, respectively. This supports that the host microbial composition or environmental factors in the gut are involved in risk of IBD. Furthermore, genetically determined high activity of the IL-23/IL-17 pathway was associated with increased risk of CD and UC. Overall, our results support that genetically determined high inflammatory response was associated with increased risk of both CD and UC.     

Mucosal Healing Did Not Predict Sustained Clinical Remission in Patients with IBD after Discontinuation of One-Year Infliximab Therapy

Aim

To assess the endoscopic activity and Clinical activity after a one-year period of infliximab therapy and to evaluate the association between mucosal healing and need for retreatment after stopping infliximab in patients with Inflammatory bowel disease (IBD).

Methods

The data from 109 patients with Crohn’s disease (CD) and 107 patients with Ulcerative colitis (UC) received one-year infliximab were assessed. The primary endpoint of the study was the proportion of clinical remission, mucosal healing and full remission in IBD after the one-year period of maintenance infliximab therapy. The secondary endpoint was the frequency of relapses in the next year.

Results

A total of 84.4% (92/109) CD patients and 81.3% (87/107) UC patients achieved clinical remission, 71.56% (78/109) of CD patients and 69.16% (74/107) of UC patients achieved mucosal healing, 56.88% (62/109) of CD patients and 54.21% (58/107) of UC patients achieved full remission at the end of the year of infliximab therapy. Infliximab therapy was restarted in the 10.19% (22/216) patients (13 CD, 9 UC) who achieved mucosal healing, and 13.89% (30/216) patients (18 CD, 12 UC) who achieved clinical remission and 6.48% (14/216) patients (8 CD, 6 UC) who achieved full remission had to be retreated within the next year. Neither clinical remission nor mucosal healing was associated with the time to restarting Infliximab therapy in IBD.

Conclusion

Mucosal healing did not predict sustained clinical remission in patients with IBD in whom the infliximab therapies had been stopped. And stopping or continuing infliximab therapy may be determined by assessing the IBD patient’s general condition and the clinical activity.     

IBD5 is a general risk factor for inflammatory bowel disease: replication of association with Crohn disease and identification of a novel association with ulcerative colitis

Inflammatory bowel disease (IBD) refers to complex chronic relapsing autoimmune disorders of the gastrointestinal tract that have been traditionally classified into Crohn disease (CD) and ulcerative colitis (UC). We have previously reported that genetic variation within a 250-kb haplotype (IBD5) in the 5q31 cytokine gene cluster confers susceptibility to CD in a Canadian population. In the current study, we first replicated this association by examining 368 German trios with CD and demonstrating, by transmission/disequilibrium testing (TDT), that the same haplotype is associated with CD (chi2=5.97; P=.007). Our original association study focused on the role of IBD5 in CD; we next explored the potential contribution of this locus to UC susceptibility in 187 German trios. Given the TDT results in the present cohort with UC, IBD5 may also act as a susceptibility locus for UC (chi2=8.10; P=.002). We then examined locus-locus interactions between IBD5 and CARD15, a locus reported elsewhere to confer risk exclusively to CD. Our current results indicate that the two loci act independently to confer risk to CD but that these two loci may behave in an epistatic fashion to promote the development of UC. Moreover, IBD5 was not associated with particular clinical manifestations upon phenotypic stratification in the current cohort with CD. Taken together, our results suggest that IBD5 may act as a general risk factor for IBD, with loci such as CARD15 modifying the clinical characteristics of disease.     

Does psychological status influence clinical outcomes in patients with inflammatory bowel disease (IBD) and other chronic gastroenterological diseases: An observational cohort prospective study

Background

Whether there is a temporal relationship between psychological problems and clinical outcomes in patients with diseases of the digestive tract has not been widely researched. Thus, our aims were 1) To observe and compare prospectively clinical outcomes in relation to psychological co-morbidity in patients with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and chronic hepatitis C (HCV) and, 2) To test the hypothesis that patients with psychological co-morbidities are less likely to have a satisfactory response to standard treatment at 12 months.

Methods

Overall, 139 patients were enrolled in this observational cohort prospective study. Over the ensuing year, physical and psychological measures were made at baseline and after 12 months (HADS, SCL90, SF-12 and disease activity measures). A logistic regression was conducted to observe any relationship between baseline characteristics and patients' clinical outcomes after 12 months.

Results

Overall, there was no relationship between psychological status and quality of life at baseline and relapse at 12 months (p > 0.05). However, patients with inactive disease at baseline were at lower risk of relapse after 12 months (OR = 0.046, CI: 0.012–0.178). No significant relationship was found between psychological problems such as depression/anxiety and a total number of relapses in the IBD group. However, interestingly, patients with an active disease at baseline tended to have a greater number of relapses (OR = 3.07, CI: 1.650–5.738) and CD participants were found at lower risk of relapse than UC participants (OR = 0.382, CI: 0.198–0.736).

Conclusion

In contrast to previous investigations, this study suggests that there is no temporal relationship between psychological problems at baseline and clinical outcomes over time. Longer and larger prospective studies are needed to better understand this result.     

The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients

Susceptibility to inflammatory bowel disease (IBD) has a strong genetic component. The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be associated with IBD in some studies. In this case-control study we determined the association between the BsmI VDR gene polymorphism and IBD in patients with Crohn's disease (CD) and ulcerative colits (UC). Three hundred seventy-nine Jewish Israeli patients with IBD, 228 with CD (129 Ashkenazi and 99 non-Ashkenazi), and 151 patients with UC (72 Ashkenazi, 79 non-Ashkenazi) were studied. The control group included 495 healthy blood donors (352 non-Ashkenazi and 143 Ashkenazi). All subjects were genotyped for the BsmI VDR gene polymorphism. The frequency of the BB genotype was higher in Ashkenazi patients with UC compared to Ashkenazi controls (0.21 vs. 0.11, p = 0.042, odds ratio 2.27, 95% confidence interval [CI] 1.06-4.9). There were no differences in the prevalence of the BB genotype or the B allele between ethnically matched patients with CD and UC. Nor were there differences in the BB genotype or B allele frequencies between CD patients and ethnically matched controls. The BsmI VDR gene polymorphism is associated with increased susceptibility to UC in Israeli Ashkenazi patients with UC.     

Prevalence of the factor V Leiden mutation in human inflammatory bowel disease with different activity

BACKGROUND: the developmental mechanism of inflammatory bowel disease (IBD) in patients is unknown, but it may be influenced by different environmental and genetical factors. AIMS of this study were: (1) to classify the IBD patients according the disease activity; and (2) to determine the presence of factor V Leiden mutation in IBD patients. PATIENTS AND METHODS: the observation was carried out in 49 patients with Crohn's disease (CD) and 29 patients with ulcerative colitis (UC). None of them had a history of thrombotic episodes. IBD was diagnosed by conventional clinical, endoscopic, radiological and histological criteria. The factor V Leiden mutation was detected by the polymerase chain reaction (PCR) method. Crohn's disease activity index (CDAI) was evaluated using the method of the National Cooperative Crohn's Disease Study. We determined the UC disease activity according to Truelove-Witts classification. RESULTS: The prevalence of factor V Leiden mutation was increased in both populations of the patients to compare it with healthy persons (14.28 and 27.58% vs. 5.26%, n=7/49 and 8/29 vs. 3/57). The statistical analysis did not show a significant relationship between the CDAI or the Truelove-Witts grade in UC and the presence of Leiden mutation. CONCLUSION: the presence of factor V Leiden mutation probably has a role in the development of IBD. Our results suggest a higher prevalence of this mutation in Central European patients than in Southern, Northern Europe or America, may be due to the genetical differences of these populations.     

Probiotics are a good choice in remission of inflammatory bowel diseases: A meta analysis and systematic review

Altered gut bacteria and bacterial metabolic pathways are two important factors in initiation and progression of inflammatory bowel disease (IBD). However, efficacy of probiotics in remission of patients with IBD has not been characterized. This study was performed on the studies that specifically assessed the efficacy of probiotics in attaining clinical response on patients with various types of IBD. The efficacy of variant species of probiotics in different conditions and the influence of study quality in outcomes of randomized controlled trials (RCTs) were also assessed. The RCTs were collected by searching in MEDLINE Web of Science and Google scholar. Then all studies were abstracted in abstraction form and the outcomes were analyzed with fixed‐effect and mixed‐effect models for assessment of efficacy of variant species of probiotics in subgroups of IBDs. Analysis of 9 trials showed that probiotics had not significant effect on Crohn's disease (CD) (p = 0.07) but analysis of 3 trials in children with IBD revealed a significant advantage (p < 0.01). Analysis of 18 trials revealed that probiotics in patients with Ulcerative colitis (UC) in different conditions have significant effects (p = 0.007). VSL#3 probiotics in patients with UC had significant effect (p < 0.01). Combination of Lactobacillus probiotic, prebiotics had significant effect (p = 0.03) only in patients with UC. Combination of Saccharomyces boulardii, Lactobacillus, and VSL#3 probiotics in CD had also a trend for efficiency (p = 0.057). In children with IBD, the combination of Lactobacillus with VSL#3 probiotics had significant effect (p < 0.01). Probiotics are beneficial in IBD, especially the combination ones in UC.

     

Mucosa-Associated Faecalibacterium prausnitzii Phylotype Richness Is Reduced in Patients with Inflammatory Bowel Disease

Faecalibacterium prausnitzii depletion in intestinal diseases has been extensively reported, but little is known about intraspecies variability. This work aims to determine if subjects with gastrointestinal disease host mucosa-associated F. prausnitzii populations different from those hosted by healthy individuals. A new species-specific PCR-denaturing gradient gel electrophoresis (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprint F. prausnitzii populations in biopsy specimens from 31 healthy control (H) subjects and 36 Crohn''s disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness of F. prausnitzii subtypes was lower in inflammatory bowel disease (IBD) patients than in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]), which were shared by all groups of patients. Their distribution and the presence of some disease-specific F. prausnitzii phylotypes allowed us to differentiate the populations in IBD and CRC patients from that in H subjects. At the level of a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD patients (P = 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P = 0.005). This study reveals that even though the main members of the F. prausnitzii population are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases. This approach may serve as a basis for addressing the suitability of F. prausnitzii phylotypes to be quantified as a putative biomarker of disease and depicting the importance of the loss of these subtypes in disease pathogenesis.