Role of nutrition in acute and long-term therapy of chronic inflammatory bowel diseases

The clinical picture and course of inflammatory bowel disease are influenced by nutritional abnormalities and malnutrition. Interest at present concentrates on high-fibre low-refined sugar diets, elimination diets with identification of specific food intolerance and low-residue diets. All three failed to show significant positive effects on the course of the disease, need for hospitalisation, surgical procedures required or post-operative recurrence. Only a low lactose diet seems to be justified, since we found lactose intolerance in 25-35% of patients with inflammatory bowel disease, as compared with 5-10% in the normal population. In 25 patients with Crohn's disease (CD) a reduction in inflammatory activity and improvement of nutritional status was obtained with parenteral nutrition (PN). Nevertheless, longer follow up periods revealed no additional benefit in comparison with conventional therapies. Furthermore, the combination of PN and total bowel rest resulted in the same improvement as with PN alone. 25 patients with CD manifesting an acute phase of the condition were treated with tube feeding (TF) as primary therapy. TF reduced CD activity and improved nutritional status in 15 patients with small bowel disease, whereas the patients with colonic disease and extraintestinal manifestations did not react. A comparison of the effect of PN and TF in 10 patients with CD showed no significant difference with regard to clinical course and objective parameters. In view of the high costs and risks of complications of PN, TF is recommended as primary therapy for the acute phase of CD. The importance of substitution therapy, especially of vitamin D, is documented.     

Diet in Benign Colonic Disorders: A Narrative Review

PurposeDiet plays an important role in common benign colorectal diseases. This article reviews the evidence for diet and supplemental fiber in patients with chronic constipation, irritable bowel syndrome, inflammatory bowel disease, colonic diverticulitis, and fecal incontinence.MethodsWe performed a narrative review of the evidence for diet and supplemental fiber in patients with 5 common benign colonic diseases and summarized guideline recommendations for each condition. We generated tables of practical dietary advice by disease.FindingsDiet advice must be individualized and depends on underlying conditions, disease severity, symptom burden, and nutrition status. Guidance from a registered dietitian is highly recommended when making any dietary changes. Data from trials suggest that soluble fiber is effective for patients with chronic constipation, irritable bowel syndrome, and fecal incontinence. A diet low in select fermentable, oligo-, di-, and monosaccharides, and polyols may benefit patients with irritable bowel syndrome. Patients with inflammatory bowel disease, especially those with active disease, are at risk for malnutrition. Dietary restrictions may further increase that risk. There is limited evidence to recommend increasing or avoiding select food groups in patients with inflammatory bowel disease. Patients who have recovered from diverticulitis should adopt a prudent dietary pattern high in fruits, vegetables, whole grains, legumes, poultry, and fish.ImplicationsClinicians should counsel patients on the contribution of diet to their colorectal condition and the benefits and harms of dietary modification. Dietary advice should be practical and accompanied by realistic expectations for benefit.     

Th17-cytokine blockers as a new approach for treating inflammatory bowel disease

Anti-cytokine therapies, including the anti-TNF-α antibody-based therapies, have largely transformed the management of patients with inflammatory bowel diseases (IBD). However, benefit is seen in nearly 50% of patients, and response can wane with time. Moreover, patients treated with anti-TNF-α antibodies can develop severe side-effects and new immune-mediated diseases. Therefore enormous effort has been made by the research community to elucidate new inflammatory networks in the IBD tissue and to develop novel anti-cytokine compounds, which may act in patients who do not respond to or cannot receive anti-TNF-α therapies. In this article we review the available data supporting the pathogenic role of Th17 cytokines in IBD, and discuss whether and how inhibitors of these inflammatory mediators may enter into the therapeutic armamentarium of IBD.     

Complementary and alternative medicine for gastrointestinal disorders

Complementary and alternative medicine (CAM) is a growing area of public interest. With increasing numbers of patients using these modalities, it is essential that Western medical practitioners become familiar with the available CAM literature to facilitate better patient care. While the volume of CAM research in gastrointestinal disorders has increased, there are still few modalities for which definitive conclusions can be made. This review will provide an overview of current knowledge of CAM therapies for functional gastrointestinal disorders, inflammatory bowel disease and liver disease. An understanding of this evolving literature is useful in discussing these therapies with patients who use, or are considering using, them. As we learn more about these CAM modalities, integration of those shown to be effective into our conventional practice and avoidance of those shown to be risky or of little use will be of benefit both to patients and practitioners.     

Angiogenesis in inflammatory bowel disease

Both ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel diseases, are recognized, at the moment, as perplexing and challenging clinical entities, in which several molecules and cell types are implicated. Recent molecular evidence proposes the intestinal microvascular remodelling or angiogenesis, as a phenomenon implicated in the pathogenesis of these chronic inflammatory disorders, together with other proposed theories involved in the pathogenesis of inflammatory bowel diseases, such as genetic, microbacterial and immune factors. Intestinal damage is followed by a physiological angiogenesis, but the abnormal expression of pro- and anti-angiogenic molecules and the changes of vascular cell types could reflect a pathological vascular remodelling. Thus, the inflammation may be favoured and maintained by a pathological angiogenesis. A better understanding of the angiogenic process may facilitate the design of more effective therapies for chronic intestinal inflammation.     

Complementary,alternative, integrative and dietary therapies for children with Crohn’s disease – A systematic review

Children with diagnosed inflammatory bowel diseases such as Crohn’s disease are faced with the daunting prospect of living with a chronic disease. Besides psychological stress, children are suffering from therapy side-effects; in particular, corticosteroid therapies are problematic in the growth phase. This highlights that there is a need for less aggressive alternative therapies for children as well as adolescents living with such chronic conditions. Elemental diets are widely used and accepted therapy options. Several pediatric Crohn’s disease patients also use complementary, alternative and integrative therapies to reduce or avoid drug therapies. To survey such therapy options and their efficiency and safety, we performed a systematic literature search and screened databases (Cochrane Library, EMBASE, OvidSP, PubMed, CAMbase, CAM-QUEST, Anthromedics) from their inception to December 2019. In total, seven of 1439 studies fulfilled search criteria. Six RCTs and one retrospective controlled trial investigating elemental diets (Flexical, Elemental 028), semi-elemental diets (Pregomin), polymeric diets (Modulen IBD), whole protein based formulas, and ω-3 fatty acid supplementation were found. Data indicated that diet therapies were equal to or more effective than corticosteroid therapies when used to treat Crohn’s disease. Regrettably, we could not identify controlled studies investigating complementary, alternative and integrative medicine approaches. Our review provides an updated overview of controlled studies investigating dietary therapies used in the treatment of pediatric Crohn’s disease, and demonstrates that the current study situation does not reflect the actual use of complementary, alternative and integrative therapies. Therefore, clinical trials are necessary to estimate risks and benefits of such therapies. The review indicated that enteral diets and ω-3 fatty acid supplementation may be an effective alternative to corticosteroid treatments for children with Chron’s disease.     

炎症性肠病合并艰难梭菌感染的研究进展

艰难梭菌感染（Clostridium difficile infection,CDI）在炎症性肠病（inflammatory bowel disease,IBD）患者中的发生率不断上升。CDI明显增加IBD患者预后不良如死亡和结肠切除手术率。有关IBD合并CDI的相关研究显示,肠道微生态、免疫和遗传因素共同决定了IBD发生CDI的风险。进一步的机制研究将有助于CDI的预防和治疗。     

Self-care strategies for the management of bowel symptoms following sphincter-saving surgery for rectal cancer

The primary aim of this article is to identify the self-care strategies that patients use to manage bowel symptoms experienced following sphincter-saving surgery for rectal cancer. Comparisons will be made with self-care strategies used by patients to manage chronic fecal incontinence and the bowel symptoms associated with other chronic bowel diseases, such as irritable bowel syndrome and inflammatory bowel disease. Published studies and conceptual literature from 2000-2010 were the data sources. Three major themes emerged from the literature reflecting the self-care strategies used by patients to manage bowel symptoms: functional self-care strategies (e.g., taking medication), social activity-related self-care strategies (e.g., planning social events), and alternative self-care strategies (e.g., complementary therapies). An analysis of studies highlighted that, through the process of trial and error, patients learned the strategies that were most effective in the management of their bowel symptoms. Knowledge of such strategies will be beneficial to healthcare professionals when educating patients about effective management of bowel symptoms following sphincter-saving surgery.     

Enzymes in feces: useful markers of chronic inflammatory bowel disease

BACKGROUND: Ulcerative colitis and Crohn's disease are characterized by a chronic intestinal inflammation. Since the precise etiology is still unknown, current therapies are aimed at reducing or eliminating inflammation. METHODS: Endoscopy and histology on biopsy specimens remain the gold standard methods for detecting and quantifying bowel inflammation. These technique are expensive, invasive and not well tolerated by patients since the need of repeated examinations affects their quality of life. Although disease activity scores and laboratory inflammatory markers are widely used they showed unreliable relations with endoscopy and histology. Fecal markers have been investigated in inflammatory bowel disease (IBD) by many authors for diagnostic purposes, to assess disease activity and of risk of complications, to predict relapse or recurrence, and to monitor the effect of therapy. Many inflammatory mediators have been detected in the feces such as leukocytes, cytokines and proteins from neutrophil activation. Some of these, particularly lactoferrin and calprotectin, have been demonstrated to be useful in detecting active inflammatory bowel disease, in predicting recurrence of disease after surgery or monitoring the effects of medical therapy. Calprotectin and lactoferrin are remarkably stable and easily detect in stool using ELISA so they appear to be equally recommendable as inflammation markers in the lower gastrointestinal tract especially in IBD patients. CONCLUSION: Fecal markers are non-invasive, simple, cheap, sensitive and specific parameters and are useful to detect strointestinal inflammation.     

Therapeutic potential of infliximab in inflammatory bowel disease.

Traditional treatment approaches for patients with inflammatory bowel disease involve 1) pharmacologic management with aminosalicylates, corticosteroids, immunomodulatory agents, and antibiotics; and 2) nonpharmacologic management by surgical and dietary means. Complications and inadequate responses to current treatment modalities have resulted in the development of new and more specific biologic therapies. The proinflammatory cytokine tumor necrosis factor alpha (TNF alpha) is present in elevated concentrations in patients with inflammatory bowel disease; therefore, it has been targeted for treatment approaches. Infliximab is a chimeric, monoclonal antibody to TNF alpha developed to inhibit the interaction of TNF alpha with its receptor, to result in amelioration of inflammation. This biologic agent has received the most attention and is the most studied of those for the treatment of patients with Crohn's disease. This article reviews the symptoms of inflammatory bowel disease, the traditional treatment approaches used, the role of TNF alpha in disease pathogenesis, and the value of infliximab in treatment.     

Investigating cell therapy for inflammatory bowel disease

ABSTRACT

Introduction: Advances in immuno-modulatory therapies, including anti-TNF-α therapies, have greatly increased the chance to achieve long-term remission of inflammatory bowel disease (IBD) patients. However, as the importance of mucosal healing has been demonstrated in a number of clinical studies, new cell-based therapies that can regenerate and fully restore the intestinal mucosal functions are currently under development.

Area covered: In this review, we feature the recent challenges of cell-based therapies that are applied to the treatment of IBD. In particular, we will focus on hematopoietic stem cells (HSC), mesenchymal stem cells (MSCs) and intestinal stem cells (ISCs) as the candidate source for cell-based therapy targeted to treat IBD. The current status, as well as the expected advantages and disadvantages of those transplantations will be summarized and discussed.

Expert opinion: Transplantation of HSC, MSC and ISC may have different levels of potential in their ability to exert an immunomodulatory or pro-regenerative effect. Combined cell therapies, such as co-transplantation of MSC and ISC, may provide improved therapeutic outcome compared to transplantation of a single cell population. Those cell-based therapies may not only improve the disease activity or tissue regeneration, but may also have the potential to decrease the risk of developing colitis-associated cancers.     

Laboratory diagnosis in inflammatory bowel disease

The assessment of disease activity in inflammatory bowel disease is done using clinical parameters and various biological disease markers. Classical disease markers including erythrocyte sedimentation rate, acute phase proteins, such as orosomucoid and CRP, leukocyte and platelet counts, play an important role in the monitoring of disease activity. Furthermore, the determination of zinc, iron, ferritin, vitamin B12, and folic acid is important to avoid deficiencies in patients with severe disease or after surgeries. Stool cultures are helpful to detect bacterial or parasitic infections mimicking inflammatory bowel disease. The detection of specific antibodies such as pANCA, PAB and ASCA is helpful for the differential diagnosis Crohn's disease--ulcerative colitis.     

Extraintestinal and systemic manifestations of inflammatory bowel disease

Extraintestinal and systemic manifestations occur commonly in patients with inflammatory bowel disease, specifically ulcerative colitis and Crohn's disease, and affect most all organ systems of the body. The occurrence of such widespread manifestations strongly suggests that these disorders are systemic in nature and may have a common mechanism. Extraintestinal manifestations may be incidental findings that cause no symptoms, but more commonly complicate the management of the underlying inflammatory bowel disease, being a source of considerable morbidity and mortality. Some extraintestinal manifestations not only correlate with a specific disease state but also with the location, extent, and degree of activity and disease. Most extraintestinal manifestations found in patients with inflammatory bowel disease involving the small intestine appear to correlate with some underlying pathophysiologic mechanism.     

Exit strategies in inflammatory bowel disease: Looking beyond anti-tumor necrosis factors

The long-term management of patients with inflammatory bowel disease (IBD) is still a matter of debate, and no clear guidelines have been issued. In clinical practice, gastroenterologists often have to deal with patients in prolonged remission after immunomodulatory or immunosuppressive therapies. When planning an exit strategy for drug withdrawal, the risk of disease relapse must be balanced against the risk of drug-related adverse events and healthcare costs. Furthermore, there is still a dearth of data on the withdrawal of novel biologics, such as the anti-α4β7 integrin antibody (vedolizumab) and anti-IL12/23 antibody (ustekinumab), as well as the small molecule tofacitinib. Models for estimating the risk of disease relapse and the efficacy of retreatment should be evaluated according to the patient's age and IBD phenotype. These models should guide clinicians in programming a temporary drug withdrawal after discussing realistic outcomes with the patient. This would shift the paradigm from an exit strategy to a holiday strategy.     

Advances in the assessment of disease activity in inflammatory bowel disease

Knowledge of the severity and extent of the inflammation in inflammatory bowel diseases provides a means of determining rational therapeutic strategies in affected patients. During the past 3 decades, several clinical, laboratory, and combined indices have been proposed for the assessment of inflammatory bowel disease; refinements in radiologic methods and the availability of endoscopy and biopsy have facilitated the accurate assessment of the extent and severity of the disease. In relapsing conditions such as inflammatory bowel disease, however, the use of such procedures is limited by the radiation exposure or the relatively invasive nature of the technique. In this article, we review the proposed methods and recent advances in assessment of patients with inflammatory bowel disease; we also discuss possible strategies at the time of diagnosis, during recurrence, and in evaluation of the efficacy of drug or dietic therapy.     

未确定型炎症性肠病的临床特征分析

【目的】通过对未确定型炎症性肠病患者的临床特征进行分析加深对该型炎性肠病的认识。【方法】对2001年3月至2008年12月期间住院病人中符合炎性肠病的258例患者的临床特点进行回顾性分组分析。【结果】258例患者中未确定型炎性肠病32例（12．4％）,克罗恩病（CD）71例（27．5％）,溃疡性结肠炎（UC）155例（60．1％）。首发症状为腹泻、粘性血便、腹痛和发热。【结论】与克罗恩病及溃疡性结肠炎相比未确定型炎性肠病有一些自己的特点,有可能是一个独立病变。     

Crohn's disease and ulcerative colitis. Evaluation with double-contrast barium examination and endoscopy

Double-contrast barium examination of the colon can demonstrate the changes associated with inflammatory bowel disease more completely and specifically than the single-contrast barium study. However, endoscopy is slightly more sensitive than double-contrast examination for detection of disease. In general, between 18% and 20% of patients with Crohn's disease or ulcerative colitis may be expected to have normal radiographic findings but endoscopically detectable disease. However, most false-negative double-contrast colon studies are associated with mild or minimal findings at proctosigmoidoscopy. Although double-contrast radiography may be less sensitive than endoscopy in detection of inflammatory bowel disease, it has similar accuracy for classification and differentiation. Most studies indicate an accuracy of 95% to 98% in differentiating Crohn's disease and ulcerative colitis, due to the fact that morphologic changes detected by the double-contrast mucosal study rarely overlap in the two diseases. Double-contrast barium examination and endoscopy are complementary studies, and the use of both may provide valuable information for evaluation of patients with suspected inflammatory bowel disease.     

Low S-adenosylmethionine concentrations found in patients with severe inflammatory bowel disease.

BACKGROUND: S-adenosylmethionine is a methyl donor in many cellular reactions including detoxification of constantly produced hydrogen sulphide in the colon. A reduced capacity to detoxify hydrogen sulphide may be implicated in the pathogenesis of inflammatory bowel disease. S-adenosylmethionine could be low if this assumption is correct. We compared S-adenosylmethionine concentrations in whole blood in patients with severe and moderate inflammatory bowel disease with healthy reference persons. METHODS: S-adenosylmethionine concentrations in whole blood were measured using high-pressure liquid chromatography. Patients with Crohn's disease (n=21), ulcerative colitis (n=7) and healthy age-matched reference persons (or controls) (n=17) were studied. RESULTS: S-adenosylmethionine concentrations were significantly decreased in patients with severe inflammatory bowel disease (mean 1.10 mg/l) as compared to patients with moderate Crohn's disease and ulcerative colitis (mean 1.83 mg/l) and reference persons (mean 1.84 mg/l). Statistically significant inverse correlations were found between S-adenosylmethionine concentration and activity index (p<0.01 and R2=0.86) as well as Crohn's disease activity index (p<0.01 and R2=0.50) scores. CONCLUSIONS: Low concentrations of S-adenosylmethionine were found in patients with severe inflammatory bowel disease. Future studies will show whether S-adenosylmethionine is a marker for disease activity and a possible tool for investigation of sulphur toxicity as a causative mechanism in inflammatory bowel disease.     

Gastrointestinal inflammation in children: color Doppler ultrasonography.

We conducted this study to determine if color Doppler ultrasonography can identify increased vascularity associated with gastrointestinal inflammatory conditions and to determine if specific diagnoses can be established based on flow patterns. Twenty-five children with acute right lower quadrant pain and discharge diagnoses of inflammatory bowel processes were examined by color Doppler sonography, as an adjunct to routine gray-scale examinations. Final diagnoses included gastroenteritis (10 cases), Crohn's disease (five cases), neutropenic colitis (four cases), peritonitis (four cases), and Yersinia enterocolitis (two cases). The results of color Doppler sonography were considered positive for inflammation if increased vascularity was demonstrated in the bowel mucosa, muscularis layer, or adjacent tissues. A control group of 19 patients was examined. No sonographic abnormalities were identified in any patients in the control group. Diffuse, concentric wall thickening with increased blood flow centrally within the mucosa was seen in Crohn's disease (60%) and Yersinia enterocolitis (100%), whereas wall thickening with increased transmural vascularity was identified in neutropenic colitis (50%) and Crohn's disease (40%). In contrast, in peritonitis color Doppler sonography showed thickened bowel wall and hypervascularity within peripheral bowel wall or in adjacent soft tissues. No demonstrable bowel vascularity was seen in gastroenteritis. Our experience suggests that mucosal or transmural hypervascularity on color Doppler sonography can be seen with several inflammatory bowel processes, but it is nonspecific. However, color Doppler sonography may aid in differentiating primary bowel disease from extrinsic inflammatory conditions, such as peritonitis.