Fecal leukocyte proteins in inflammatory bowel disease and irritable bowel syndrome

The aim of this prospective study was to compare five different leukocyte proteins in feces of patients with chronic inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and healthy persons who underwent prophylactic colonoscopy. METHODS: The leukocyte proteins calprotectin, lactoferrin, lysozyme, myeloperoxidase, and PMN-elastase were determined with immunoassays in fecal samples of three consecutive feces (e.g. three days) in 40 healthy persons, 39 patients with chronic IBD (of these 21 with Crohn's disease and 18 with ulcerative colitis), and 40 patients with IBS. RESULTS: ROC curves calculated for healthy persons and patients with IBD yielded the following areas under the curves (AUCs): PMN-elastase 0.916, calprotectin 0.872, myeloperoxidase 0.750, lysozyme 0.726, and lactoferrin 0.693. The AUCs of PMN-elastase and calprotectin were not significantly different (p = 0.327), whereas PMN-elastase or calprotectin vs. the other proteins were significantly different (p < 0.001). PMN-elastase and calprotectin correlated with the endoscopically classified severity of inflammation. All fecal leukocyte markers in IBS were found in the range of the healthy persons. Data on storage stability of leukocyte proteins in fecal supernatants are given. CONCLUSION: Fecal PMN-elastase and calprotectin support the differentiation of chronic IBD from IBS and correlate with the severity of inflammation.     

Of worms,mice and man: An overview of experimental and clinical helminth-based therapy for inflammatory bowel disease

The incidence of inflammatory and autoimmune disorders is highest in well-developed countries which is directly related to their higher hygienic standards: it is suggested that the lack of exposure to helminths contributes to the susceptibility for immune-related diseases. Epidemiological, experimental and clinical data support the idea that helminths provide protection against immune-mediated diseases such as inflammatory bowel disease (IBD). The most likely mechanism for the suppression of immune responses by helminths is the release of helminth-derived immunomodulatory molecules. This article reviews the experimental and clinical studies investigating the therapeutic potential of helminth-based therapy in IBD and also focuses on the current knowledge of its immunomodulatory mechanisms of action highlighting innate as well as adaptive immune mechanisms. Identifying the mechanisms by which these helminths and helminth-derived molecules modulate the immune system will help in creating novel drugs for the treatment of IBD and other disorders that result from an overactive immune response.     

'One sip won't do any harm . . .': Temptation among women with inflammatory bowel disease/irritable bowel syndrome to engage in negative dietary behaviours, despite the consequences to their health

The purpose of this research was to explore the dietary lived experiences of university-aged women suffering from inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This paper will address the decision-making process used by these women when contemplating the consumption of dietary temptations, despite the associated negative consequences. This phenomenological study was guided by heuristic inquiry. A purposive sample of eight women, between the ages of 18 and 23 years, who were living with IBD or IBS were recruited via postings and word-of-mouth. The findings indicate that these women occasionally felt compelled to give into dietary temptations, despite the consequences to their health. The decision-making process they used when considering these negative health behaviours involved three personally controlled parameters. These three parameters included: assessing the cost–benefit relationship before engaging in these behaviours; having a physical and/or psychological reliance on medications to treat resulting symptoms; and through controlling the timing and surroundings in which they indulged in these negative dietary behaviours. The practical implications for health-care professionals treating patients with IBD or IBS are discussed.     

Clinical manifestations of vegetative dysfunction in patients with irritated bowel syndrome

The purpose of the study was to evaluate interrelations between clinical manifestations of irritated bowel syndrome (IBS) and vegetative dysfunction (VD). The subjects were 153 patients with gastroduodenal pathology: 120--with IBS, and 23--with inflammatory bowel diseases (IBD). The study found that vegetative dysfunction was associated with IBS more often than with IBD. Clinical manifestations of IBS were associated with VD syndrome (VDS), including high intensivity and frequency of abdominal pain, feeling of abdominal swelling, elevated anxiety level, and low rectal sensitivity threshold. VDS is probably one of the links of its pathogenesis. VDS is not associated with a type of intestinal passage disorder. VDS in IBS patients is often of constitutional character and is associated with lower life quality.     

'I feel as if my IBS is keeping me hostage!' Exploring the negative impact of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) upon university-aged women

The purpose of this article is to describe the negative impact of irritable bowel syndrome (IBS) and/or inflammatory bowel disease (IBD) upon university-aged women. This exploratory study was conducted using phenomenology, with heuristic inquiry as the guiding theoretical orientation. Seven women participated in an email interview and in a semistructured interview. The findings indicate that women with active IBD/IBS commonly experience an anxiety reaction, followed by an attack of illness. This attack then triggers a cascade of impact that negatively influences their emotional and physical well-being, ultimately affecting their overall quality of life. Health-care professionals can play an important role in minimizing the impact of IBD/IBS upon those affected, and possible interventions are suggested.     

A role for proteinase-activated receptor-1 in inflammatory bowel diseases

Proteinase-activated receptor-1 (PAR1), a G protein-coupled receptor activated by thrombin, is highly expressed in different cell types of the gastrointestinal tract. The activity of thrombin and of other proteinases is significantly increased in the colon of inflammatory bowel disease (IBD) patients. Since PAR1 activation in tissues other than the gut provoked inflammation, we hypothesized that PAR1 activation in the colon is involved in the pathogenesis of IBD. Here, we demonstrate that PAR1 is overexpressed in the colon of IBD patients. In mice, intracolonic administration of PAR1 agonists led to an inflammatory reaction characterized by edema and granulocyte infiltration. This PAR1 activation-induced inflammation was dependent on B and T lymphocytes. Moreover, PAR1 activation exacerbated and prolonged inflammation in a mouse model of IBD induced by the intracolonic administration of trinitrobenzene sulfonic acid (TNBS), while PAR1 antagonism significantly decreased the mortality and severity of colonic inflammation induced by TNBS and dextran sodium sulfate. In these 2 models, colitis development was strongly attenuated by PAR1 deficiency. Taken together, these results imply an important role for PAR1 in the pathogenesis of experimental colitis, supporting the notion that PAR1 inhibition may be beneficial in the context of IBD and possibly in other chronic intestinal inflammatory disorders.     

Psychosocial aspects of inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are known as inflammatory bowel disease (IBD), chronic and potentially disabling diseases, affecting about 90 to 300 per 100,000 people in the general population. Although significant gains have been made in our understanding of these diseases, particularly with respect to pathophysiology and treatment, its etiology is still unknown. IBD is a significant disease that can severely impact one's psychological and social well-being. This article reviews the literature on the psychosocial aspects of IBD. We also address the importance of conceptualizing IBD from a biopsychosocial perspective, considering psychosocial factors along with disease activity. The biopsychosocial approach offers a broadened perspective that reflects the many factors that may contribute to the expression and maintenance of IBD symptoms. Issues of concerns for patients with IBD are also discussed. Finally, we highlight the importance of establishing a collaborative therapeutic relationship between patients and their physicians, facilitating open and honest discussions acknowledging patients' fears and concerns. In doing so, much of these IBD-related issues of concerns may be ameliorated, potentially improving one's coping abilities, and lead to an improved quality of life for individuals with inflammatory bowel disease.     

Transfer of interleukin-4 and interleukin-10 in patients with severe inflammatory bowel disease of the rectum

Inflammatory bowel disease (IBD) comprises the two disorders ulcerative colitis (UC) and Crohn's disease (CD). Although the etiology is still unclear, initiation and aggravation of the inflammatory processes seem to be due to a massive local mucosal immune response. An increased number of greatly activated macrophages seems to contribute to the onset of IBD by expressing upregulated costimulatory molecules (e.g., CD80/CD86) and a cytokine profile favouring a type I proinflammatory response. The release of interleukin 2 (IL-2) and Interferon-gamma (IFN-gamma) by naive T lymphocytes predominantly stimulates cytotoxic T lymphocytes, macrophages, and natural killer (NK) cells and increases the antigen-presenting potential of all these cell types. Opposite this proinflammatory immune reaction a compensatory type II antiinflammatory response has been suggested in the inflamed mucosa, involving mainly interleukin 4 and interleukin 10. Both cytokines are able to down-regulate inflammatory mediators including tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 and favor a humoral immune response. The main goal of this clinical trial is the local liposome-mediated gene transfer of these two antiinflammatory cytokines, interleukin 4 and interleukin 10, in patients with severe IBD of the rectum. This local administration of antiinflammatory cytokines will avoid toxic systemic side effects, prevents blocking of the beneficial effects of proinflammatory cytokines, e.g., TNF-alpha in other tissue compartments and increases the local concentration of interleukin 4 and interleukin 10 over a prolonged period of time. The combined effects of IL-4 and IL-10 have been shown to shift the Th1/Th2 cell activation in favor of a Th2 immune response which seems to be essential for fighting against the inflammation and ultimative healing.     

Molecular pathogenesis of inflammatory bowel disease: genotypes, phenotypes and personalized medicine

Crohn's disease (CD) and ulcerative colitis (UC), also known as inflammatory bowel diseases (IBD), are characterized by chronic inflammation of the gastrointestinal tract. IBD is among the few complex diseases for which several genomic regions and specific genes have been identified and confirmed in multiple replication studies. We will review the different loci implicated in disease risk in the context of three proposed mechanisms leading to chronic inflammation of the gut mucosa: 1) deregulation of the innate immune response to enteric microflora or pathogens; 2) increased permeability across the epithelial barrier; and 3) defective regulation of the adaptive immune system. As our knowledge of genetic variation, analytical approaches and technology improves, additional genetic risk factors are expected to be identified. With the identification of novel risk variants, additional pathophysiological mechanisms are likely to emerge. The resulting discoveries will further our molecular understanding of IBD, potentially leading to improved disease classification and rational drug design. Moreover, these approaches and tools can be applied in the context of variable drug response with the goal of providing more personalized clinical management of patients with IBD.     

Role of in vitamin D in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder affecting 10%-22% of adults. Its development is closely related to the gut microbiota, and the inflammatory and immune responses triggered by the gut microbiota can lead to IBS. Vitamin D (VD) effectively treats IBS with fewer side effects by improving gut microbiota, immune regulation, and anti-inflammatory effects. In the future, it is necessary to carry out epidemiological studies on the relationship between VD and IBS, clinical studies on the efficacy of supplementing VD to improve IBS, and animal studies on the mechanism of VD improving IBS. Therefore, this paper discussed the relationship between VD and IBS.     

Role of intestinal subepithelial myofibroblasts in inflammation and regenerative response in the gut

Inflammatory bowel disease (IBD) is characterized by an ongoing mucosal inflammation caused by a dysfunctional host immune response to commensal microbiota and dietary factors. In the pathophysiology of IBD, mesenchymal cells such as intestinal subepithelial myofibroblasts (ISEMF) affect the recruitment, retention and activation of immune cells. Mesenchymal cells also promote resolution of inflammatory activity accompanied with balanced repair processes. The transient appearance of mesenchymal cells is a feature of normal wound healing, but the persistence of these cells is associated with tissue fibrosis. Recent studies suggest that mesenchymal cells derived from bone marrow (BM) stem cells play a crucial role in intestinal repair and fibrosis. This article focuses on recent knowledge about ISEMF in the field of immune response inflammation and repair. Two major topics were documented: interaction between interleukin (IL)-17-secreting CD4+ cells (Th-17 cells) and about role of BM-derived stem cells in mucosal regenerative response via differentiation to ISEMF. Recent therapeutic strategies targeting BM stem cells for IBD patients were also documented.     

Defective expression of gp180, a novel CD8 ligand on intestinal epithelial cells, in inflammatory bowel disease.

Previous studies support a role for intestinal epithelial cells (IEC) as antigen-presenting cells in mucosal immune responses. T cells activated by IEC are CD8+, suppressor in function, and dependent upon CD8-associated p56lck activation. A 180-kD glycoprotein (gp180) recognized by mAbs B9 and L12 has been identified and shown to be important in CD8+ T cell activation by IEC. Since IEC derived from patients with inflammatory bowel disease (IBD) are incapable of activating CD8+ T cells, we asked whether this correlated with gp180 expression. While frozen sections of normal bowel revealed bright gp180 staining on all IEC, both inflamed and uninflamed ulcerative colitis (UC) specimens showed patchy staining. In Crohn's disease (CD), staining was faint to absent. Flow cytometry confirmed immunohistochemical data. The staining patterns correlated with the ability of IEC to activate CD8-associated p56lck. Normal IEC induced phosphorylation of p56lck in CD8alpha but not CD4+ transfectants. In contrast, both UC and CD IEC activated CD4 and, to a much lesser extent, CD8-associated p56lck. Thus, gp180 expression by IBD IEC appears to be altered, and correlates with a functional alteration of lck activation. This defect may reflect a more proximal event in the pathogenesis of IBD.     

Effects of gender on irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders, with prevalence between 10% and 15%, which predominates in female. Two-thirds of IBS patients are female, and the prevalence of condition range from 14% to 24%. In addition to sex hormone, the other factors, i.e.) visceral perception, autonomic nervous system and pharmacological treatment response, are associated with gender differences in IBS. Recent studies indicate that pain thresholds to visceral stimulation are lower in females with IBS compared with males with IBS. It is also indicated that males with IBS have greater sympathovagal balance in response to visceral stimulation. Further elucidation of gender differences in IBS may contribute to treatment of IBS.     

Role of adherent invasive Escherichia coli in pathogenesis of inflammatory bowel disease

Gut microbiota imbalances play an important role in inflammatory bowel disease (IBD), but no single pathogenic microorganism critical to IBD that is specific to the IBD terminal ileum mucosa or can invade intestinal epithelial cells has been found. Invasive Escherichia coli (E. coli) adhesion to macrophages is considered to be closely related to the pathogenesis of inflammatory bowel disease. Further study of the specific biological characteristics of adherent invasive E. coli (AIEC) may contribute to a further understanding of IBD pathogenesis. This review explores the relationship between AIEC and the intestinal immune system, discusses the prevalence and relevance of AIEC in Crohn's disease and ulcerative colitis patients, and describes the relationship between AIEC and the disease site, activity, and postoperative recurrence. Finally, we highlight potential therapeutic strategies to attenuate AIEC colonization in the intestinal mucosa, including the use of phage therapy, antibiotics, and anti-adhesion molecules. These strategies may open up new avenues for the prevention and treatment of IBD in the future.     

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome

Irritable bowel syndrome (IBS), which is characterized by recurrent abdominal pain and disordered bowel habits, is one of the most common functional bowel disorders. IBS is a substantial burden on both patient health-related quality of life and healthcare costs. Several pathophysiologic mechanisms have been postulated for the occurrence of IBS, including altered gastrointestinal motility, visceral hypersensitivity, changes in gut permeability, immune activation, gut-brain dysregulation, central nervous system dysfunction, and changes in the gut microbiota. Of note, both qualitative and quantitative differences have been observed in the gut microbiota of a population with IBS versus a healthy population. Because of the substantial interest in the gut microbiota and its role as a therapeutic target in IBS, this article provides an overview of specific interventions with the potential to modulate the gut microbiota in IBS, including elimination diets, prebiotics, probiotics, synbiotics, and nonsystemic antibiotics. Although probiotics and synbiotics are generally well tolerated, differences in the composition and concentration of different bacterial species and inclusion or exclusion of prebiotic components varies widely across studies and has prevented strong recommendations on their use in IBS. For nonsystemic antibiotics, rifaximin is indicated in the United States for the treatment of IBS with diarrhea in adults and has been shown to be efficacious and well tolerated in well-designed clinical trials. Overall, more consistent evidence is needed regarding the efficacy and safety of elimination diets, prebiotics, probiotics, and synbiotics for the treatment of patients with IBS. Furthermore, additional well-designed studies are needed that examine alterations in the gut microbiota that occur with these interventions and their potential associations with clinical symptoms of IBS.     

Neurotensin is a proinflammatory neuropeptide in colonic inflammation

The neuropeptide neurotensin mediates several intestinal functions, including chloride secretion, motility, and cellular growth. However, whether this peptide participates in intestinal inflammation is not known. Toxin A, an enterotoxin from Clostridium difficile, mediates pseudomembranous colitis in humans. In animal models, toxin A causes an acute inflammatory response characterized by activation of sensory neurons and intestinal nerves and immune cells of the lamina propria. Here we show that neurotensin and its receptor are elevated in the rat colonic mucosa following toxin A administration. Pretreatment of rats with the neurotensin receptor antagonist SR-48, 692 inhibits toxin A-induced changes in colonic secretion, mucosal permeability, and histologic damage. Exposure of colonic explants to toxin A or neurotensin causes mast cell degranulation, which is inhibited by SR-48,692. Because substance P was previously shown to mediate mast cell activation, we examined whether substance P is involved in neurotensin-induced mast cell degranulation. Our results show that neurotensin-induced mast cell degranulation in colonic explants is inhibited by the substance P (neurokinin-1) receptor antagonist CP-96,345, indicating that colonic mast activation in response to neurotensin involves release of substance P. We conclude that neurotensin plays a key role in the pathogenesis of C. difficile-induced colonic inflammation and mast cell activation.     

Molecular pathogenesis of inflammatory bowel disease: Genotypes,phenotypes and personalized medicine

Crohn's disease (CD) and ulcerative colitis (UC), also known as inflammatory bowel diseases (IBD), are characterized by chronic inflammation of the gastrointestinal tract. IBD is among the few complex diseases for which several genomic regions and specific genes have been identified and confirmed in multiple replication studies. We will review the different loci implicated in disease risk in the context of three proposed mechanisms leading to chronic inflammation of the gut mucosa: 1) deregulation of the innate immune response to enteric microflora or pathogens; 2) increased permeability across the epithelial barrier; and 3) defective regulation of the adaptive immune system. As our knowledge of genetic variation, analytical approaches and technology improves, additional genetic risk factors are expected to be identified. With the identification of novel risk variants, additional pathophysiological mechanisms are likely to emerge. The resulting discoveries will further our molecular understanding of IBD, potentially leading to improved disease classification and rational drug design. Moreover, these approaches and tools can be applied in the context of variable drug response with the goal of providing more personalized clinical management of patients with IBD.     

Symptom burden in inflammatory bowel disease: Rethinking conceptual and theoretical underpinnings

Farrell D, Savage E. International Journal of Nursing Practice 2010; 16 : 437–442
Symptom burden in inflammatory bowel disease: Rethinking conceptual and theoretical underpinnings Symptom control is fundamental to the nursing management of inflammatory bowel disease (IBD). However, symptom control can be problematic for individuals with IBD, which could result in symptom burden. Symptom burden is an evolving concept in the discipline of nursing and to date little is known about how the defining characteristics of this concept have been applied to symptom research in IBD. In this discussion paper, the concept of symptom burden and the theory of unpleasant symptoms are explored as a basis for understanding symptom research in IBD. This is followed by a critical examination of previous symptom research in IBD. Our conclusion is that there is a need to rethink conceptual and theoretical underpinnings of symptom burden when researching IBD to take account of its defining characteristics, namely symptom severity, frequency and duration, quality and distress. Research knowledge on these defining characteristics will be important to inform nursing assessment of symptom burden in clinical practice.     

犬尿喹啉酸在肠易激综合征中的作用机制

肠易激综合征(irritable bowel syndrome，IBS) 是一种常见的肠道功能紊乱性疾病，以持续或间歇性腹痛及排便习惯改变为主要临床表现，常伴有焦虑、抑郁等精神症状，严重影响患者生活质量。目前，IBS的病因及发病机制尚不明确，现有研究表明IBS是由内脏感觉异常、肠道感染与炎症反应、肠道菌群失调、社会心理等多种因素共同作用的结果。近期研究表明IBS患者中存在肠道菌群-犬尿氨酸(kynurenine, KYN)代谢紊乱，且KYN代谢产物犬尿喹啉酸(kynurenic acid，KA)与炎症反应、疼痛刺激及心理症状相关，在IBS中可能起到抗炎、缓解疼痛等保护性作用，有望成为诊断和治疗IBS的新方法。本文就KYN代谢途径及其代谢产物KA在IBS中的作用机制作一综述，以期为临床相关专业人员提供参考和借鉴。     

Low mast cell density in the human duodenal mucosa from chronic inflammatory duodenal bowel disorders is associated with defective villous architecture

BACKGROUND: Mast cells (MC) have recently been implicated in the processes of tissue homeostasis, remodeling and repair. DESIGN: In this study, the total and tryptase-reactive mast cell populations were quantified in the duodenal mucosa of 27 subjects suffering from chronic inflammatory bowel disorders. Mast cell density was both related to the general villous architecture (normal or defective) and to the microvascular density in the duodenal mucosa. RESULTS: Total mast cell and tryptase-positive mast cell subpopulation densities were found to be significantly reduced in the samples with defective villous architecture in comparison with those exhibiting a normal villous profile. In these last samples, a relevant proportion of mucosal mast cells exhibited ultrastructural features of secretory activity, in particular piecemeal degranulation. Finally, no correlation was established between microvascular density and tryptase activity, as it has been previously demonstrated in other pathological conditions. CONCLUSIONS: Overall, these findings indicate a significant correlation between mast cell density and the duodenal mucosal architecture.