Factors affecting vitamin D deficiency in active inflammatory bowel diseases

BackgroundHypovitaminosis D is prevalent in inflammatory bowel disease (IBD) and may be associated with disease activity.AimThis study evaluated vitamin D (VitD) status in an Italian cohort of IBD patients, not taking VitD supplementation. We investigated risk factors for VitD deficiency and its correlation with disease activity.MethodsVitD levels were measured in 300 consecutive outpatients (42% with Crohn’s Disease (CD) and 58% with ulcerative colitis (UC), 56% male) from a tertiary referral center. Data from the IBD cohort were compared with those of 234 healthy controls, matched by sex, age, and the month in which VitD levels were measured.ResultsThe mean VitD level in IBD patients was significantly lower than in controls (18.9 ng/ml vs. 25 ng/ml, p < 0.001) when accounting for gender, age, and season. VitD deficiency was present in 62% of IBD patients. Risk factors for deficiency were: age <40 and ≥60 years, winter, previous surgery, C-reactive protein (CRP) ≥0.5 mg/dl, and erythrocyte sedimentation rate ≥20 mm/h. In multivariate analysis, VitD levels were negatively influenced by disease location and CRP in UC.ConclusionsAlthough VitD deficiency was more prevalent than expected in healthy controls living in a Mediterranean country not at high risk of hypovitaminosis D, it was more common and severe in IBD patients. This study also found an association between VitD status and disease activity     

Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases

AIM: To investigate the effect of vitamin D (VD) concentrations and VD supplementation on health related quality of life in inflammatory bowel disease (IBD) patients.METHODS: A cohort of 220 IBD patients including 141 Crohn’s disease (CD) and 79 ulcerative colitis (UC) patients was followed-up at a tertiary IBD center. A subgroup of the cohort (n = 26) took VD supplements for > 3 mo. Health related quality of life was assessed using the short IBD questionnaire (sIBDQ). VD serum concentration and sIBDQ score were assessed between August and October 2012 (summer/autumn period) and between February and April 2013 (winter/spring period). The mean VD serum concentration and its correlation with disease activity of CD were determined for each season separately. In a subgroup of patients, the effects of VD supplementation on winter VD serum concentration, change in VD serum concentration from summer to winter, and winter sIBDQ score were analyzed.RESULTS: During the summer/autumn and the winter/spring period, 28% and 42% of IBD patients were VD-deficient (< 20 ng/mL), respectively. In the winter/spring period, there was a significant correlation between sIBDQ score and VD serum concentration in UC patients (r = 0.35, P = 0.02), with a trend towards significance in CD patients (r = 0.17, P = 0.06). In the winter/spring period, VD-insufficient patients (< 30 ng/mL) had a significantly lower mean sIBDQ score than VD-sufficient patients; this was true of both UC (48.3 ± 2.3 vs 56.7 ± 3.4, P = 0.04) and CD (55.7 ± 1.25 vs 60.8 ± 2.14, P = 0.04) patients. In all analyzed scenarios (UC/CD, the summer/autumn period and the winter/spring period), health related quality of life was the highest in patients with VD serum concentrations of 50-59 ng/mL. Supplementation with a median of 800 IU/d VD day did not influence VD serum concentration or the sIBDQ score.CONCLUSION: VD serum concentration correlated with health related quality of life in UC and CD patients during the winter/spring period.     

Role of the intestinal microbiota and fecal transplantation in inflammatory bowel diseases

Ulcerative colitis and Crohn's disease are the two major types of inflammatory bowel disease (IBD). Despite intensive study, it is still challenging because the precise etiology and pathogenesis remains unclear. Studies have shown that IBD is associated with changes in the composition of intestinal microbiota, as either a cause or a consequence of abnormal host immune response in genetic susceptible population. Two specific microorganisms (Mycobacterium avium subsp. paratuberculosis and Escherichia coli) get more widely studied, but till now no single microorganism has been identified as the only pathogen. Genetic susceptibility data also suggest impaired handling of bacteria as well as an improper immune response to potential pathogens. The microbiota provides new therapeutic methods, and fecal microbiota transplantation may restore the balance of intestinal flora to supplement or optimize the current therapies.     

Serum vitamin B12 and folate status in patients with inflammatory bowel diseases

BackgroundThe aims of this study were to investigate the prevalence of serum vitamin B₁₂ and folate abnormalities in patients with inflammatory bowel diseases (IBD) and to identify risk factors associated with B₁₂ and folate abnormalities in this entity.Methods138 patients with IBD (45 Crohn's disease and 93 ulcerative colitis) and 53 healthy subjects were enrolled into the study. Fasting serum B₁₂ and folic acid levels were measured and clinical data regarding inflammatory bowel diseases were gathered.ResultsWhile the mean serum B₁₂ concentration in CD patients was 281 ± 166 pg/ml, the mean serum vitamin B₁₂ concentration in UC patients was 348 ± 218 pg/ml (p = 0.224). The number of patients with vitamin B₁₂ deficiency in the CD group was greater than the number of patients with UC [n = 10 (22%) vs. n = 4 (7.5%), p = 0.014]. The number of patients (n = 10, 22%) with B₁₂ deficiency in the CD group was also greater than controls (n = 4, 7.5%) (p = 0.039). With regard to folate levels, the median serum folate level was 7.7 ± 5.3 ng/ml in CD patients, 8.6 ± 8.3 ng/ml in UC patients and 9.9 ± 3.3 ng/ml in the control group (p = n.s.). Patients with a prior ileocolonic resection had an abnormal B₁₂ concentration compared to patients without surgery (p = 0.008). In CD patients, ileal involvement was the only independent risk factor for having a low folate level.ConclusionSerum vitamin B₁₂ and folate deficiencies are common in patients with CD compared to UC patients and controls. In CD patients, prior small intestinal surgery is an independent risk factor for having a low serum vitamin B₁₂ level.     

Fatigue is not associated with vitamin D deficiency in inflammatory bowel disease patients

AIM To investigate if vitamin D deficiency is associated with fatigue in patients with inflammatory bowel disease(IBD).METHODS IBD patients were recruited from nine hospitals in the southeastern and western regions of Norway to participate in a multicenter cross-sectional study lasting from March 2013 to April 2014. Data were collected by interviews, from medical records and laboratory tests. The Fatigue Questionnaire(FQ) was used to measure fatigue. Linear and logistic regression models were applied to explore the possible association between vitamin D deficiency and total fatigue scores and chronic fatigue, respectively. The analyses were adjusted for age, gender, disease activity, depressive symptoms and sleep disturbance.RESULTS In total, 405 patients were included in the analyses, of which 227(56%) had Crohn's disease(CD) and 178(44%) had ulcerative colitis(UC). Vitamin D deficiency( 50 nmol/L) was present in half(203/405) of the patients. Chronic fatigue was reported by 116(29%) of all included patients with substantial fatigue reported by 194(48%). Vitamin D levels were neither associated with total fatigue nor with chronic fatigue. Higher total fatigue scores and chronic fatigue were both associated with increased disease activity scores in patients with UC and CD, but not with increased CRP or fecal calprotectin. In UC patients, female gender was associated with fatigue in the univariate analysis, but no such difference was found when adjusted for elevated disease activity scores. Sleep disturbance and more depressive symptoms were associated with total fatigue scores in both UC and CD patients, but with chronic fatigue only in CD patients.CONCLUSION In this study, no significant association between fatigue and vitamin D deficiency in IBD patients was revealed.     

Characteristics of inflammatory bowel diseases in patients with concurrent immune-mediated inflammatory diseases

Patients with inflammatory bowel disease (IBD) are more likely to have concurrent immune-mediated inflammatory diseases (IMIDs) than those without IBD. IMIDs have been observed to alter the phenotype and outcomes of IBD in recent studies. Several studies have found that IBD patients with concurrent IMIDs may have more extensive or severe disease phenotypes, and are considered to be at increased risk of requiring biologics and IBD-related surgeries, suggesting that having multiple IMIDs is a poor prognostic factor for IBD. Furthermore, IBD patients with primary sclerosing cholangitis and Takayasu arteritis are reported to have unique endoscopic phenotypes, suggesting concurrent IMIDs can influence IBD phenotype with specific intestinal inflammatory distributions. In this review, we discuss the pathogenesis, disease phenotypes, and clinical outcomes in IBD patients with concomitant IMIDs.     

Serum vitamin D and colonic vitamin D receptor in inflammatory bowel disease

AIM: To determine serum vitamin D levels and colonic vitamin D receptor(VDR) expression in inflammatory bowel disease(IBD) and non-IBD patients and correlate these with histopathology.METHODS: Puerto Rican IBD(n = 10) and non-IBD(n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire and provided a serum sample and a colonic biopsy of normal-appearing mucosa. For IBD patients, an additional biopsy was collected from visually diseased mucosa. Serum vitamin D levels were measured by ultra-performance liquid chromatography and mass spectrometry. Hematoxylin and eosin stained tissue sections from colonic biopsies were classified histologically as normal or colitis(active/inactive), and scored for the degree of inflammation present(0-3, inactive/absent to severe). Tissue sections from colonic biopsies were also stained by immunohistochemistry for VDR, for which representative diagnostic areas were photographed and scored for staining intensity using a 4-point scale.RESULTS: The IBD cohort was significantly younger(40.40 ± 5.27, P 0.05) than the non-IBD cohort(56.70 ± 1.64) with a higher prevalence of vitamin D deficiency(40% vs 20%, respectively) and insufficiency(70% vs 50%, respectively). Histologic inflammation was significantly higher in visually diseased mucosa from IBD patients(1.95 ± 0.25) than in normalappearing mucosa from control patients(0.25 ± 0.08, P 0.01) and from IBD patients(0.65 ± 0.36, P 0.05) and correlated inversely with VDR expression in visually diseased colonic tissue from IBD patients(r =-0.44, P 0.05) and from IBD patients with Crohn's disease(r =-0.69, P 0.05), but not in normal-appearing colonic tissue from control patients or IBD patients. Control and IBD patient serum vitamin D levels correlated positively with VDR expression in normal colon from control and IBD patients(r = 0.38, P 0.05) and with patient age(r = 0.54, P 0.01). CONCLUSION: Levels of serum vitamin D correlate positively with colonic VDR expression in visually normal mucosa whereas inflammation correlates negatively with colonic VDR expression in visually diseased mucosa in Puerto Rican patients.     

Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease

Background and Aims: The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be linked to inflammatory bowel disease (IBD). Many studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about the genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms (Apa I, Taq I, Bsm I, Fok I) with IBD in Iran. Methods: In this case control designed study 150 patients with ulcerative colitis, 80 patients with Crohn's disease and 150 Age and Sex matched healthy controls from Iranian origin were enrolled. These patients were referred to a tertiary center during a two‐year period (2004–2006). Assessment of VDR gene polymorphisms was performed by the polymerase chain reaction—restriction fragment length polymorphism (PCR‐RFLP) method. The genotype–phenotype association for these polymorphisms was analyzed. Results: Only the frequency of the Fok I polymorphism was significantly higher in ulcerative colitis and Crohn's groups. The frequency of the polymorphic allele f was higher in ulcerative colitis and Crohn's patients comparing with controls (P = 0.011 and P < 0.001, respectively). The f/f genotype was also significantly more frequent (P < 0.001), while the F/F genotype was less presented in Crohn's patients compared to controls (P < 0.001). No genotype–phenotype association was observed with any mutations. Conclusions: This study suggests a probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population.     

维生素D与炎症性肠病的研究进展

由于广泛的免疫调节及抗微生物作用,维生素D与自身免疫疾病的关系受到越来越多的关注.而对于炎症性肠病,尽管根本机制不明,但关于其发病已形成基本共识,即在一定环境因素下,由共生茵及其所产生致炎因子作用于免疫缺陷的个体,产生持续的免疫反应.由于维生素D对固有免疫、适应性免疫的调节作用及其作用方式,以及其可调控上皮细胞抑菌肤的产生,参与肠道微生态的平衡,有理由认为活性维生素D的产生和作用的不足可能参与了炎症性肠病的发病,同时维生素D可能是很有前景的预防和治疗炎症性肠病的药物.     

Intestinal superinfections in patients with inflammatory bowel diseases

BackgroundIntestinal superinfections may occur in the setting of inflammatory bowel diseases (IBD), complicating the clinical picture and triggering flares of disease.AimsTo report our experience with intestinal superinfections in IBD patients over a three-year period.MethodsCharts of patients hospitalized for moderate-to-severe active disease during the observation period were reviewed, and data of patients with flares due to infections collected and analyzed.ResultsOverall, 15 out of 113 IBD patients (13.3%) had flare-ups related to intestinal infections; 143 acute flare-ups were thus documented, with 17 episodes (12%) related to infective agents, represented by Campylobacter jejuni (3 infections), Clostridium difficile (7 infections), and Cytomegalovirus (7 infections). All but two infections occurred in ulcerative colitis patients, and all responded to appropriate treatment.ConclusionsIntestinal superinfections may complicate the clinical picture of IBD patients, increasing the diagnostic and therapeutic burden. Appropriate early diagnostic and therapeutic measures are thus needed in these patients.     

Role of Smad7 in inflammatory bowel diseases

Crohn''s disease and ulcerative colitis, the major forms of inflammatory bowel diseases (IBD) in man, are complex diseases in which genetic and environmental factors interact to promote an excessive mucosal immune response directed against normal components of the bacterial microflora. There is also evidence that the pathologic process is due to defects in counter-regulatory mechanisms, such as those involving the immunosuppressive cytokine transforming growth factor (TGF)-β1. Indeed, studies in human IBD tissues and murine models of colitis have documented a disruption of TGF-β1 signalling marked by a block in the phosphorylation of Smad3, a signalling molecule associated with the activated TGF-β receptor, due to up-regulation of Smad7, an intracellular inhibitor of Smad3 phosphorylation. Knock-down of Smad7 with a specific antisense oligonucleotide restores TGF-β1/Smad3 signalling, thus resulting in a marked suppression of inflammatory cytokine production and attenuation of murine colitis. These findings together with the demonstration that Smad7 antisense oligonucleotide is not toxic when administered in mice have paved the way for the development of a Smad7 antisense oligonucleotide-based pharmaceutical compound that is now ready to enter the clinics. In this article we review the available data supporting the pathogenic role of Smad7 in IBD and discuss whether and how Smad7 antisense therapy could help dampen the ongoing inflammation in IBD.     

Role of the microbiota in inflammatory bowel diseases

Studying the role of the human microbiome as it relates to human health status has revolutionized our view of microbial community contributions to a large number of diseases, particularly chronic inflammatory disorders. The lower gastrointestinal (GI) tract houses trillions of microbial cells representing a large diversity of species in relatively well-defined phylogenetic ratios that are associated with maintenance of key aspects of host physiology and immune homeostasis. It is not surprising, therefore, that many GI inflammatory diseases, including inflammatory bowel disease (IBD), are associated with substantial changes in the composition of these microbial assemblages, either as a cause or consequence of host inflammatory response. Here we review current knowledge in the emerging field of human microbiome research as it relates to IBD, specifically focusing on Crohn's disease (CD) and ulcerative colitis (UC). We discuss bacteriotherapeutic efforts to restore GI microbial assemblage integrity via probiotic supplementation of IBD patients, and speculate on future directions for the field.     

Role of the endothelium in inflammatory bowel diseases

Inflammatory bowel diseases(IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the disease.At the core of these alterations are endothelial cells,whose continual adjustments in structure and function coordinate vascular supply,immune cell emigration,and regulation of the tissue environment.Expansion of the endothelium in IBD(angiogenesis),mediated by inflammatory growth factors,cytokines and chemokin...     

Characteristics of intestinal dendritic cells in inflammatory bowel diseases

BACKGROUND & AIMS: Dendritic cells (DCs) recognize and respond to microbial structures using pattern recognition receptors, including Toll-like receptors (TLRs). In the intestine, DCs are pivotal in tolerance induction and direct the differentiation of T cells. We aimed to identify changes in intestinal DCs that may underlie the dysregulated immune response to enteric bacteria that occurs in patients with inflammatory bowel disease (IBD). METHODS: DCs were identified in freshly isolated lamina propria mononuclear cells by multicolor flow cytometry in patients with IBD and controls. Expression of TLR2, TLR4, and the activation/maturation marker CD40 was assessed by cell surface labeling. Production of cytokines (interleukin [IL]-12, IL-6, and IL-10) was assessed in the absence of exogenous stimulation by intracellular staining of permeabilized cells. RESULTS: In healthy controls, few intestinal DCs expressed TLR2 or TLR4, in contrast to blood DCs. DC expression of both TLRs was significantly enhanced in Crohn's disease and ulcerative colitis. DCs from inflamed tissue of patients with Crohn's disease expressed significantly higher levels of the maturation/activation marker CD40. Elevated levels of CD40 on DCs were decreased after treating patients with anti-tumor necrosis factor alpha. In Crohn's disease, but not ulcerative colitis, more colonic DCs produced IL-12 and IL-6. The number of IL-10-producing DCs did not differ significantly between patients with IBD and controls. CONCLUSIONS: In IBD, DCs are activated, their expression of microbial recognition receptors is up-regulated, and more DCs produce pathologically relevant cytokines. Intestinal DCs are likely to be key initiators or perpetuators of the inflammatory response that characterizes IBD.     

Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy

Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were <20 ng/mL and 21–29 ng/ml, respectively. Patients were sub-grouped according to biologic therapy. A multivariate analysis was performed. Two-hundred patients, including 136 with a rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p < 0.0001), in either rheumatic diseases (78.7 vs 41 %; p < 0.0001) or IBD (75 vs 50 %; p = 0.03) group. At multivariate analysis, only biologic therapy was independently associated with vitamin D deficit (OR 4.61; p = 0.001). Patients with vitamin D deficiency/insufficiency had hypocalcemia more frequently than controls (22.8 vs 10.9 %; p = 0.03), while PTH values did not differ significantly. This study finds that the prevalence of vitamin D deficiency/insufficiency was very high in patients with either rheumatic diseases or IBD receiving a biologic therapy.     

Role of the intestinal barrier in inflammatory bowel disease

A critical function of the intestinal mucosa is to form a barrier that separates luminal contents from the interstitium. The single layer of intestinal epithelial cells （IECs） serves as a dynamic interface between the host and its environment. Cell polarity and structural properties of the epithelium is complex and is important in the development of epithelial barrier function. Epithelial cells associate with each other via a series of intercellular junctions. The apical most intercellular junctional complex referred to as the Apical Junction Complex （AJC） is important in not only cell-cell recognition, but also in the regulation of paracellular movement of fluid and solutes. Defects in the intestinal epithelial barrier function have been observed in a number of intestinal disorders such as inflammatory bowel disease （IBD）. It is now becoming evident that an aberrant epithelial barrier function plays a central role in the pathophysiology of IBD. Thus, a better understanding of the intestinal epithelial barrier structure and function in healthy and disease states such as IBD will foster new ideas for the development of therapies for such chronic disorders.     

New concepts in intestinal imaging for inflammatory bowel diseases

In the last decade, multiple imaging technologies have been developed that improve visualization of the mucosal, mural, and perienteric inflammation associated with inflammatory bowel diseases. Whereas these technologies have traditionally been used to detect and stage suspected enteric inflammation, we review new, emerging roles in detecting clinically occult inflammation (in asymptomatic patients) and inflammatory complications, predicting response prior to therapy, assessing response after therapy, and enteric healing. We compare the relative performance of these technologies in detecting inflammation, focusing on their advantages and disadvantages and how they might complement each other. We also discuss their potential benefits for patients and clinical trials, reviewing technologic developments and areas of research that could provide important insights into the pathophysiology of inflammatory bowel diseases-related enteric inflammation.     

维生素D在肺部疾病中的作用

除了维持钙盐代谢和骨骼的稳态以外,研究发现维生素D还可调控包括机体防御,炎症,免疫,损伤修复等在内的多种生理和病理生理过程.流行病学资料表明,血清低水平的维生素D与肺功能受损、炎症反应和感染性疾病相关.因此,支气管哮喘、慢性阻塞性肺疾病和肺部感染性疾病都可能与维生素D水平有关,但具体的机制尚不明确.因此,本文通过文献回顾,概述维生素D在肺部疾病,包括支气管哮喘、慢性阻塞件肺疾病、肺结核和呼吸道感染中的作用.