真菌菌群在炎症性肠病中的作用研究进展CSCD

炎症性肠病(inflammatory bowel disease,IBD)包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD),是消化道的慢性复发性炎症性疾病,多年来IBD与肠道菌群的关系备受关注[1-2],其发病率在全球范围内呈上升趋势[3]。IBD的发病机制是遗传易感性、环境影响和肠道屏障受损等多因素之间相互作用的结果[4-5]。     

益生菌在炎症性肠病中的治疗作用

炎症性肠病(inflammatory bowel disease,IBD)包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。随着对肠道微生物群在IBD发病机制中作用的认识不断深入,近年来益生菌广泛应用于IBD治疗。大量临床试验结果表明,益生菌治疗IBD的疗效主要体现在对UC和贮袋炎的治疗,对CD的疗效不明确。益生菌治疗IBD可能通过促进肠道微生物群平衡、改善肠道屏障功能、调节肠道黏膜免疫及营养物质代谢等途径。     

益生菌在儿童炎症性肠病中的应用

炎症性肠病(inflammatory bowel disease,IBD)是一种原因不明的慢性非特异性肠道炎性疾病,主要包括溃疡性结肠炎(ulcerative colitis,UC)、克罗恩病(Crohn′s disease,CD)和未定型的炎症性肠病(IBD-unclassified,IBDU)。随着对肠道微生物与IBD关系认识的不断加深,许多研究发现肠道菌群的生态失调在IBD的发病中起着重要作用。益生菌在儿童IBD治疗中具有良好前景,但仍缺乏有效的证据来确证益生菌疗效,并指导临床对益生菌的种类和剂量等进行选择。现有研究表明,益生菌对儿童IBD的治疗具有特异性,在诱导和维持UC缓解效果明显,但在诱导CD缓解、维持CD缓解和预防术后并发症及复发方面效果并不理想。     

TL1A/DR3在炎症性肠病发病机制中的研究进展

炎症性肠病(inflammatory bowel disease,IBD)的发病机制至今尚不明确,近年来研究发现,肿瘤坏死因子超家族(tumor necrosis factor super family,TNFSF)参与了炎症性肠病的发病过程。其中,肿瘤坏死因子样配体1A(TNFliked ligand 1A,TL1A)与其受体DR3(death receptor 3)在肠道免疫炎症反应的多个环节中发挥重要作用。本文就TL1A/DR3在炎症性肠病发病机制中的研究进展作一综述。     

P2X7受体与炎症性肠病北大核心CSCD

P2X7受体与炎症密切相关,且在肠道细胞广泛表达。动物实验表明,ATP/P2X7信号主要介导加重肠炎,众多细胞参与这一作用,包括巨噬细胞、树突状细胞、T细胞、肥大细胞以及肠道神经元等。也有证据表明在弓形虫引起的肠炎中,P2X7信号则发挥抑制炎症的作用,其具体机制还有待进一步研究。本文就P2X7受体与炎症性肠病(inflammatory bowel disease,IBD)的相关研究进展作一综述,希望能为P2X7受体与IBD的进一步研究提供指导和借鉴。     

肠道菌群在炎症性肠病发病中的作用

炎症性肠病(IBD)是一种非特异性肠道炎症性疾病,其病因和发病机制尚不完全明确。肠道菌群作为一个非常复杂的微生态系统,在IBD的患病机制中扮演着非常重要的角色。本研究就肠道微生态系统、肠道菌群与IBD发病的关系以及肠道菌群调控对IBD的作用的最新进展进行综述。     

潘氏细胞与炎症性肠病研究进展

<正>潘氏细胞(paneth cells,PCs)是小肠腺的特征性细胞,可分泌防御素等多种抗菌物质,抑制肠道细菌过度繁殖,在维持肠道内稳态、参与固有免疫方面发挥重要作用。炎症性肠病(inflammatory bowel disease,IBD)主要包括克罗恩病(crohn's disease,CD)和溃疡性结肠炎(ulcerative colitis,UC),其发病机制复杂,受环境因素、遗传因素及肠道菌群等多种因素的影响,主要表现为肠道免疫系统对肠道菌群的不良免疫反应。近年来,有关PCs与IBD的相关性研究较多,现本文就其研究进展作一综述如下。     

粪菌移植在儿童炎症性肠病中的应用

炎症性肠病(IBD)是一种病因尚不明确的非特异性肠道炎症性疾病。越来越多的证据表明肠道菌群失调与IBD的发生发展密切相关。粪菌移植是通过各种方式将健康捐赠者的粪便菌群移植入患者消化道内,旨在重建患者肠道菌群从而达到对肠道内外疾病治疗的目的。肠道微生物稳态及失调在疾病发生发展中发挥作用,其中包括炎症性肠病(IBD)。越来越多的研究报道了FMT在IBD中的治疗作用,现主要阐述粪菌移植在儿童IBD中的应用。     

多巴胺能系统与炎症性肠病

多巴胺(dopamine,DA)是一种儿茶酚胺类的神经递质。多项研究表明多巴胺能信号通路是促进中枢神经系统和免疫系统之间平衡的关键因素,某些免疫细胞自身可以产生和释放DA。DA受体广泛表达于多种免疫细胞,DA能系统受损可能影响免疫稳态,从而影响自身免疫性疾病的发生和进展。这使得DA和炎症性肠病(inflammatory bowel disease,IBD)的研究成为热点,DA受体成为治疗某些炎症性疾病的药理靶点。据报道肠道微生物也可以合成DA,而肠道菌群失衡在IBD的发病中扮演着重要的角色,但肠道微生物、DA和IBD三者的关系并不十分明确。本文综述了多巴胺能系统、肠道菌群与IBD的关联,为进一步了解DA的免疫调节作用,以及开发与DA相关的药物提供理论基础。     

益生菌治疗炎症性肠病的研究进展

炎症性肠病（inflammatory bowel disease,IBD）主要包括溃疡性结肠炎（ulcerative olitis,UC）和Crohn＇s病（Crohn＇s disease,CD）,近年来随着人们生活水平的提高以及饮食结构的变化,该病在我国的发病率逐年上升.目前研究认为IBD是由基因的易感性,环境因素激发和肠道免疫系统失调等多种因素交互作用引起的消化系统自身免疫性慢性炎症疾病.应用免疫抑制剂作为临床上治疗该病的主要手段已经有了很大的发展,却仍然存在着价格昂贵,毒副作用强,而且并不是对所有患者都有效等问题.长期使用抗生素则因容易引起肠道细菌耐药而导致菌群失调,往往使得IBD的病情更加复杂.临床研究表明IBD患者肠道内存在着严重的菌群失调,通过给予益生菌对局部的微生态环境进行调节,可使病情缓解.本文从炎症性肠病的病因学出发,对目前应用益生菌治疗IBD及其治疗机制的研究进展进行综述.     

Chemokine and cytokine levels in inflammatory bowel disease patients

Crohn’s disease (CD) and ulcerative colitis (UC), two forms of inflammatory bowel disease (IBD), are chronic, relapsing, and tissue destructive lesions that are accompanied by the uncontrolled activation of effector immune cells in the mucosa. Recent estimates indicate that there are 1.3 million annual cases of IBD in the United States, 50% of which consists of CD and 50% of UC. Chemokines and cytokines play a pivotal role in the regulation of mucosal inflammation by promoting leukocyte migration to sites of inflammation ultimately leading to tissue damage and destruction. In recent years, experimental studies in rodents have led to a better understanding of the role played by these inflammatory mediators in the development and progression of colitis. However, the clinical literature on IBD remains limited. Therefore, the aim of this study was to evaluate systemic concentrations of key chemokines and cytokines in forty-two IBD patients with a range of disease activity compared to levels found in ten healthy donors. We found a significant increase in an array of chemokines including macrophage migration factor (MIF), CCL25, CCL23, CXCL5, CXCL13, CXCL10, CXCL11, MCP1, and CCL21 in IBD patients as compared to normal healthy donors (P < 0.05). Further, we also report increases in the inflammatory cytokines IL-16, IFN-γ, IL-1β and TNF-α in IBD patients when compared to healthy donors (P < 0.05). These data clearly indicate an increase in circulating levels of specific chemokines and cytokines that are known to modulate systemic level through immune cells results in affecting local intestinal inflammation and tissue damage in IBD patients. Blockade of these inflammatory mediators should be explored as a mechanism to alleviate or even reverse symptoms of IBD.     

Carcinoembryonic antigen (CEACAM) family members and Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic intestinal inflammatory condition with increasing incidence worldwide and whose pathogenesis remains largely unknown. The collected evidence indicates that genetic, environmental and microbial factors and a dysregulated immune response are responsible for the disease. IBD has an early onset and long term sufferers present a higher risk of developing colitis associated cancer (CAC). The carcinoembryonic antigen-related adhesion molecules (CEACAM) are a subgroup of the CEA family, found in a range of different cell types and organs including epithelial cells in the intestine. They can act as intercellular adhesions molecules for e.g. bacteria and soluble antigens. CEACAMs are involved in a number of different processes including cell adhesion, proliferation, differentiation and tumour suppression. Some CEACAMs such as CEACAM1, CEACAM5 and CEACAM6 are highly associated with cancer and are even recognised as valid clinical markers for certain cancer forms. However, their role in IBD pathogenesis is less understood. The purpose of this review is to provide a comprehensive summary of published literature on CEACAMs and intestinal inflammation (IBD). The interactions between CEACAMs and bacteria adhesion in relation to IBD pathophysiology will be addressed and potential new therapeutic and diagnostic opportunities will be identified.     

The multifaceted role of CARD9 in inflammatory bowel disease

Inflammatory bowel disease (IBD) involves a dysregulated immune response to the gut microbiota. Emerging evidence has demonstrated that dysfunctions in caspase recruitment domain‐containing protein 9 (CARD9) may contribute to the pathogenesis of IBD. Interestingly, an allelic series of Card9 variants have both a common predisposing and rare protective function in IBD patients. In this review, we provide mechanistic insights into the role of the CARD9 adaptor molecule in intestinal inflammation and determine a potential CARD9‐targeting therapeutic approach against IBD.     

The Role of Cyclophilins in Inflammatory Bowel Disease and Colorectal Cancer

Cyclophilins (Cyps) is a kind of ubiquitous protein family in organisms, which has biological functions such as promoting intracellular protein folding and participating in the pathological processes of inflammation and tumor. Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are two common intestinal diseases, but the etiology and pathogenesis of these two diseases are still unclear. IBD and CRC are closely associated, IBD has always been considered as one of the main risks of CRC. However, the role of Cyps in these two related intestinal diseases is rarely studied and reported. In this review, the expression of CypA, CypB and CypD in IBD, especially ulcerative colitis (UC), and CRC, their relationship with the development of these two intestinal diseases, as well as the possible pathogenesis, were briefly summarized, so as to provide modest reference for clinical researches and treatments in future.     

The role of heme oxygenase and carbon monoxide in inflammatory bowel disease

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a chronic and recurrent inflammatory disorder of the intestinal tract. Since the precise pathogenesis of IBD remains unclear, it is important to investigate the pathogenesis of IBD and to evaluate new anti-inflammatory strategies. Recent evidence suggests that heme oxygenase-1 (HO-1) plays a critical protective role during the development of intestinal inflammation. In fact, it has been demonstrated that the activation of HO-1 may act as an endogenous defensive mechanism to reduce inflammation and tissue injury in various animal intestinal injury models induced by ischemia-reperfusion, indomethacin, lipopolysaccharide-associated sepsis, trinitrobenzene sulfonic acid or dextran sulfate sodium. In addition, carbon monoxide (CO) derived from HO-1 has been shown to be involved in the regulation of intestinal inflammation. Furthermore, administration of a low concentration of exogenous CO has a protective effect against intestinal inflammation. These data suggest that HO-1 and CO may be novel therapeutic molecules for patients with gastrointestinal inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 and CO in intestinal inflammation.     

Lymphatic pump function in the inflamed gut

The role of the lymphatic circulation to actively remove fluid, cells, proteins, and other particles from the interstitium to prevent mounting edema is well appreciated, but whether and how this function is compromised during inflammation has been scarcely investigated. We discuss here the mechanisms of lymphatic pumping and their modulation in inflammatory conditions or by inflammatory mediators in the context of inflammatory bowel disease (IBD), an ensemble of disorders typically described with abnormal or dysfunctional intestinal or mesenteric lymphatic vessels. We report our findings showing impaired mesenteric lymphatic contractile activity in an animal model of intestinal inflammation that recapitulates some features of IBD and suggests a role for prostanoids in this dysfunction. With the knowledge that prostaglandin E(2) and prostacyclin are implicated in IBD pathogenesis and induce a potent inhibition of lymphatic pumping, we established the pharmacological profile for these prostaglandin receptors in mesenteric lymphatic vessels and their respective role in pumping inhibition. Inhibition of mesenteric lymphatic pumping during inflammation may be a cause of edema, compromised immune response, and granuloma associated with IBD.     

Role of sphingosine-1-phosphate receptors in vascular injury of inflammatory bowel disease

Sphingosine-1-phosphate receptors (S1PRs) have an impact on the intestinal inflammation of inflammatory bowel disease (IBD) by regulating lymphocyte migration and differentiation. S1PR modulators as an emerging therapeutic approach are being investigated for the treatment of IBD. However, the role of S1PRs in intestinal vessels has not drawn much attention. Intestinal vascular damage is one of the major pathophysiological features of IBD, characterized by increased vascular density and impaired barrier function. S1PRs have pleiotropic effects on vascular endothelial cells, including proliferation, migration, angiogenesis and barrier homeostasis. Mounting evidence shows that S1PRs are abnormally expressed on intestinal vascular endothelial cells in IBD. Unexpectedly, S1PR modulators may damage intestinal vasculature, for example increase intestinal bleeding; therefore, S1PRs are thought to be involved in the regulation of intestinal vascular function in IBD. However, little is understood about how S1PRs regulate intestinal vascular function and participate in the initiation and progression of IBD. In this review, we summarize the pathogenic role of S1PRs in and the underlying mechanisms behind the intestinal vascular injury in IBD in order for improving IBD practice including S1PR-targeted therapies.     

Lymphatic vessel contractile activity and intestinal inflammation

Edema is a consistent observation in inflammatory bowel disease (IBD), and immune responses are inevitable in inflammation. Because the lymphatic system is an integral part of both tissue fluid homeostasis and immune reactions, it is likely that lymphatics play a role in the complex etiology of IBD. Despite the consistent findings that the lymphatic system is altered during gastrointestinal inflammation, the majority of studies conducted on the disease only mention the lymphatic system in passing. The effects of inflammatory mediators on lymphatic vessel function also remain poorly defined, despite its essential role in immunity and prevention of tissue edema. Processes allowing effective lymph transport are altered during inflammation, however, the mode of alteration and reason why lymphatics are ineffective in inflammatory reactions need to be further investigated. In addition, these processes have not yet been examined in an appropriate animal model and little has been done using in vivo methods of investigation in any model of gastrointestinal inflammation. This paper reviews the role of the lymphatic system in intestinal inflammation, as well as the role of the inflammatory products in mediating lymphatic contractile function.     

Tumor necrosis factor and lymphotoxin in regulation of intestinal inflammation

Ulcerative colitis and Crohn’s disease are the major forms of inflammatory bowel disease. Cytokines of the tumor necrosis factor (TNF) family play an important role in the regulation of intestinal inflammation. In this review, we discuss the function of key cytokines of this family–TNF and lymphotoxin (LT)–in mucosal healing, IgA production, and in control of innate lymphoid cells (ILCs), novel regulators of mucosal homeostasis in the gut. TNF plays a central role in the pathogenesis of inflammatory bowel diseases (IBD). LT regulates group 3 of ILCs and IL-22 production and protects the epithelium against damage by chemicals and mucosal bacterial pathogens. In addition, we discuss major mouse models employed to study the mechanism of intestinal inflammation, their advantages and limitations, as well as application of TNF blockers in the therapy for IBD.