益生菌治疗溃疡性结肠炎的研究现状

大量动物试验和临床研究显示,肠道菌群的改变在溃疡性结肠炎(Ulcerative colitis,UC)的发病机制中起重要作用,缓解肠道菌群失调是治疗UC的新策略。其中,在临床上应用益生菌(Probiotics)防治UC,实验研究显示其可能是通过生物拮抗作用、改善肠黏膜屏障功能及调节肠道黏膜免疫等机制参与防治UC。就常见益生菌、益生菌治疗UC的机制以及其疗效等研究现状进行了综述。     

益生菌和思密达辅助治疗溃疡性结肠炎的研究进展

溃疡性结肠炎（ulcerative colitis,UC）是一种反复发作腹痛、腹泻、黏液便和血便的直肠和结肠慢性非特异性炎症性疾病,其发病原因和致病机制仍不明确。UC尚无确切根治方案,目前临床上以维持缓解、预防复发为治疗手段。近年来研究表明,UC与肠道菌群失调、肠道屏障功能缺陷具有密切联系,于是,关于益生菌制剂及思密达对UC治疗作用的研究备受重视。本文对近年来益生菌制剂及思密达辅助治疗UC的研究进展进行综述。     

肠道菌群-阿尔茨海默病防治的新靶标

阿尔茨海默病(Alzheimer's disease,AD)是一种渐进性中枢神经系统退行性疾病,其发病机制仍未完全阐明.近年来,随着菌群-肠-脑轴研究的兴起,肠道菌群在AD发生和发展中的作用日益得到重视.本文综述了AD患者的肠道菌群特征,肠道菌群影响AD的主要途径及益生菌、抗生素和饮食等对AD患者的干预作用,为制定靶向...     

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。     

益生菌对不同年龄人群功能性便秘治疗效果的研究进展

功能性便秘是一种常见的功能性胃肠道疾病。患者通常伴有腹痛、腹胀等现象,严重影响患者生活质量,其治疗仍具有挑战性。近年来研究发现肠道菌群紊乱与功能性便秘的发生发展密切相关。益生菌能够调节肠道菌群平衡,加强肠道生物的屏障功能,参与免疫系统发挥作用,为治疗功能性便秘提供了新思路。本文对益生菌治疗功能性便秘的现状进行综述,阐明功能性便秘的发生机制、功能性便秘患者的肠道菌群变化及益生菌治疗不同年龄人群功能性便秘的效果,为益生菌在功能性便秘患者中的应用提供参考。     

肠道微生物群落与炎症性肠病关系研究进展

目的炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC）,以持续性肠道非特异性炎症为特征,通常反复发作、迁延不愈,临床上仍无特效性的治疗手段。IBD确切的发病机制尚不清楚,涉及免疫、环境及遗传等因素,这些因素共同诱导肠道炎症、黏膜损伤和修复。肠道微生物群落及其代谢产物、宿主基因易感性及肠道黏膜免疫三方面共同参与了IBD的发病机制。本文从消化道微生态角度出发,对目前IBD相关的肠道微生物群落研究现状、宿主-微生物间免疫应答及益生菌治疗等内容进行探讨。     

益生菌与宿主疾病关系的研究进展

人类肠道中含有的多种微生物,称为肠道菌群,它们对宿主的健康起着至关重要的作用。肠道菌群的组成包括细菌、病毒和真核生物,已经被证明与宿主健康有密切的联系,尤其是其中的益生菌。益生菌通过多种途径发挥作用,包括与宿主微生物的相互作用、抵御病原菌的定殖、改善肠道屏障功能、调节免疫功能、产生相关代谢产物,在宿主的代谢、免疫和神经系统中发挥有益作用。综述益生菌的作用机制,讨论了近年来益生菌应用临床研究实例以更好地理解其对疾病风险和健康可持续性的贡献,将为新的治疗干预和疾病预防策略提供参考。     

益生菌治疗变应性鼻炎的研究进展CSCD

变应性鼻炎(allergic rhinitis,AR)是临床上的多发病和常见病,其发病率逐年升高。近年来,随着分子生物学的不断发展,越来越多的研究认为AR的发病机制可能和肠道菌群有关。因此,肠道菌群和AR之间的关系逐渐成为过敏性疾病的研究热点,而益生菌在AR中所发挥的治疗作用也备受关注。研究表明Th17/Treg细胞、树突状细胞(dendritic cells,DCs)及Toll样受体(Toll-like receptors,TLRs)参与AR的发病。本文综述益生菌对Th17/Treg细胞的免疫调节作用、促进耐受性的DCs活性以及TLRs对DCs和Th17/Treg细胞的刺激作用的相关研究,探讨AR的调节机制,并阐明益生菌可能是治疗AR的潜在新方法,为AR的肠道微生态研究提供一定的理论依据。     

益生菌的免疫调节作用及其相关应用研究进展

益生菌的定义来自希腊语,益生菌是指:当摄入足够的剂量时可以对宿主产生有益影响的活的微生物。目前,全球对益生菌及其相关制剂的研究日益受到重视,益生菌在食品、营养品及医药领域的研究也不断深入,益生菌的免疫调节机制主要包括黏膜屏障作用、增强单核—巨噬细胞的吞噬作用、促进sIgA生成等。此外,益生菌还应用于临床相关疾病的治疗,改善受损肝脏的功能,缓解肠易激综合征的临床症状,通过调节脂肪代谢及胰岛素敏感性预防2型糖尿病的发生,预防结直肠肿瘤细胞生长及减轻肠道炎症等。本文主要就益生菌的上述相关研究进展进行综述,为益生菌的研究及相关应用提供参考。     

从肠道菌群角度认识阿尔茨海默病的潜在发病机制

过去10年中,人们逐渐认识到肠道微生物群的多样性及菌群平衡在维护宿主健康中发挥的作用。肠道微生物及其代谢产物通过一系列的生化、免疫和生理功能环节与宿主进行交流,从而影响宿主的稳态和健康。阿尔茨海默病(Alzheimer’s disease,AD)是一种复杂的神经退行性疾病,其易感性和发展过程受年龄、遗传和表观遗传等因素的影响。研究发现,肠道微生物群的紊乱(组成改变和易位)与神经系统疾病(AD)有关,胃肠道通过肠脑轴与中枢神经系统进行沟通,包括对神经的直接作用、内分泌途径和免疫调控方式。动物模型、粪便菌群移植及益生菌干预为肠道菌群与AD的相关性提供了证据。外漏的细菌代谢产物可能直接损害神经元功能,也可能诱发神经炎症,促进AD的发病。本文主要综述了肠道微生物群与AD的关联和作用机制,以期为通过改善肠道菌群结构预防AD的可能干预措施提供依据。     

The development of gut immune responses and gut microbiota: effects of probiotics in prevention and treatment of allergic disease

The infant's immature intestinal immune system develops as it comes into contact with dietary and microbial antigens in the gut. The evolving indigenous intestinal microbiota have a significant impact on the developing immune system and there is accumulating evidence indicating that an intimate interaction between gut microbiota and host defence mechanisms is mandatory for the development and maintenance of a balance between tolerance to innocuous antigens and capability of mounting an inflammatory response towards potential pathogens. Disturbances in the mucosal immune system are reflected in the composition of the gut microbiota and vice versa. Distinctive alterations in the composition of the gut microbiota appear to precede the manifestation of atopic disease, which suggests a role for the interaction between the intestinal immune system and specific strains of the microbiota in the pathogenesis of allergic disorders. The administration of probiotics, strains of bacteria from the healthy human gut microbiota, have been shown to stimulate antiinflammatory, tolerogenic immune responses, the lack of which has been implied in the development of atopic disorders. Thus probiotics may prove beneficial in the prevention and alleviation of allergic disease.     

Effects of probiotics, probiotic DNA and the CpG oligodeoxynucleotides on ovalbumin-sensitized Brown-Norway rats via TLR9/NF-κB pathway

The aim of the study was to investigate the effect of living probiotics, probiotic DNA and the synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODN) on both immune response and intestinal barrier function in ovalbumin-sensitized rat and the underlying mechanisms. Brown-Norway rats were orally sensitized with ovalbumin, and living probiotics, probiotic DNA extraction, synthetic CpG-ODN or non-CpG ODN control was administered. In the living probiotics, probiotic DNA and CpG-ODN groups, the allergic response was significantly inhibited, the Th1/Th2 cytokine balance was shifted away from Th2 side, the percentage of CD4(+) CD25(+high) Treg cells was increased, and the intestinal barrier function was improved. The levels of toll-like receptor (TLR) 9 mRNA and nuclear factor (NF)-κB activity, as well as the IκB-α phosphorylation (p-IκB-α) was significantly increased in these three intervention groups compared with the OVA-positive group, whereas no such effects were found in the non-CpG ODN control group. These data show that the probiotic genomic DNA and the synthetic CpG-ODN was comparable with living probiotics in preventing food allergic response by immune modulation and intestinal barrier function enhancement, and the activation of TLR9/NF-κB signal pathway might be involved in this process.     

益生菌防治特应性皮炎的研究进展

特应性皮炎(atopic dermatitis,AD)是会反复发作、具有明显遗传倾向性的慢性炎症性皮肤病,发病率逐年增高.AD的发病机制主要为遗传性或获得性皮肤屏障受损引起的皮肤微生态失衡和变应原渗漏,激活对应的炎症反应,造成"屏障受损-炎症反应"的恶性循环.AD的传统治疗方法多采用糖皮质激素和免疫抑制剂,但其副作用的...     

Atopic dermatitis: molecular mechanisms,clinical aspects and new therapeutical approaches

Atopic dermatitis (AD) is a genetically determinated, chronic inflammatory skin disorder associated with cutaneous erythema and severe pruritus, affecting 10-15% of children with increasing incidence and socio-economical relevance. Frequently, AD is associated with development of allergic rhinitis and/or asthma later in childhood. In most of patients AD is associated with a sensitization to food and/or environmental allergens and increased serum-IgE, while only a fewer percentage missed links to the classical atopic diathesis. Currently investigated pathogenetic aspects of AD include imbalanced Th1/Th2 responses, altered prostaglandin metabolism, intrinsic defects in the keratinocyte function, delayed eosinophil apoptosis, and IgE-mediated facilitated antigen presentation by epidermal dendritic cells. An inflammatory response of the two-phase-type and the effects of staphylococcal superantigens (SAgs) are also reported. At present a standardized cure of AD and a consensus on therapeutical approach of the severe form of the disease have not been established. Current management of AD is directed to the reduction of cutaneous inflammation and infection, mainly by S. aureus, and to the elimination of exacerbating factors (irritants, allergens, emotional stresses). Since patient with AD show abnormalities in immunoregulation, therapy directed to adjustment of their immune function could represent an alternative approach, particularly in the severe form of the disease. In this review, we analyse the clinical and genetic aspects of AD, the related molecular mechanisms, and the immunobiology of the disease, focusing our attention on current treatments and future perspectives on this topic.     

The role of innate immunity activation in house dust mite allergy

House dust mite (HDM) allergy is a frequent inflammatory disease found worldwide. Although allergen-specific CD4(+) Th2 cells orchestrate the HDM allergic response, notably through induction of IgE directed towards mite allergens, recent studies have demonstrated that innate immunity activation also plays a critical role in HDM-induced allergy pathogenesis. HDM allergens can not only be considered proteins that induce adaptive Th2-biased responses in susceptible subjects but also as strong activators of innate immune cells, including skin keratinocytes and airway epithelial cells. The contribution of microbial adjuvant factors, derived from HDM carriers or the environment, is also essential in such cell stimulation. This review highlights how HDM allergens, together with microbial compounds, promote allergic responses through pattern recognition receptor-dependent pathways.     

Compartmental imbalance and aberrant immune function of blood CD123+ (plasmacytoid) and CD11c+ (myeloid) dendritic cells in atopic dermatitis

Atopic dermatitis (AD) is a pruritic, chronically relapsing skin disease in which Th2 cells play a crucial role in cutaneous and extracutaneous immune reactions. In humans, CD11c+CD123- myeloid dendritic cells (mDC) and CD11c-CD123+ plasmacytoid DC (pDC) orchestrate the decision-making process in innate and acquired immunity. Since the number and function of these blood dendritic cell (DC) subsets reportedly reflect the host immune status, we studied the involvement of the DC subsets in the pathogenesis of AD. Patients with AD had an increased DC number and a low mDC:pDC ratio with pDC outnumbering mDC in the peripheral blood compared with normal subjects and psoriasis patients (a Th1 disease model group). The mDC:pDC ratio was correlated with the total serum IgE level, the ratio of IFN-gamma-producing blood cells:IL-4-producing blood cells, and the disease severity. In vitro allogeneic stimulation of naive CD4+ cells with atopic DC showed that the ability of pDC for Th1 induction was superior or comparable to that of mDC. In skin lesions, pDC infiltration was in close association with blood vessels expressing peripheral neural addressins. Therefore, compartmental imbalance and aberrant immune function of the blood DC subsets may deviate the Th1/Th2 differentiation and thus induce protracted allergic responses in AD.     

Skin-infiltrating CD8+ T cells initiate atopic dermatitis lesions

Skin lesions in the allergic form of atopic dermatitis (AD) are induced by allergen-specific T cells that infiltrate the skin at the site of allergen exposure. Although Th2-type CD4+ T cells appear to be crucial in AD pathophysiology, little is known about the contribution of CD8+ T cells in the development of the allergic skin inflammation. In the present study, we have analyzed the respective role of CD8+ and CD4+ T cells in the development of AD skin lesions in a mouse model of allergen-induced AD. In sensitized mice, CD8+ T cells are rapidly and transiently recruited to the allergen-exposed site and initiate the inflammatory process leading to skin infiltration with eosinophils and Th1/Th2-producing cells. CD8+ T cell-depleted mice show no inflammation, demonstrating that these cells are mandatory for the development of AD. In contrast, CD4+ T cell-depleted mice develop a severe form of eczema. Furthermore, adoptive transfer of CD8+ T cells from sensitized mice into naive recipient mice leads to skin inflammation soon after allergen exposure. These data indicate that allergen-primed CD8+ T cells are required for the development of AD-like lesions in mice.     

Epicutaneous Exposure to Staphylococcal Superantigen Enterotoxin B Enhances Allergic Lung Inflammation via an IL-17A Dependent Mechanism

ATOPIC DERMATITIS (AD) IS THE INITIAL STEP OF THE ATOPIC MARCH: the progression from AD to allergic rhinitis and asthma. There is a close association between skin barrier abnormalities and the development of AD and the atopic march. One of cardinal features of AD is that the lesional skin of the majority of AD patients is chronically colonized with Staphylococcus aureus with half isolates producing superantigen enterotoxin B (SEB). Although diverse roles of SEB in the pathogenesis and severity of AD have been recognized, whether SEB contributes to the dermal inflammation that drives lung inflammation and airway hyperresponsiveness (AHR) has not been examined. Here we show a novel role of S. aureus superantigen SEB in augmenting allergen ovalbumin (Ova) induced atopic march through an IL-17A dependent mechanism. When mice epicutaneously (EC) sensitized with allergen Ova, addition of topical SEB led to not only augmented systemic Th2 responses but also a markedly exaggerated systemic Th17/IL-17 immune environment. The ability of SEB in enhancing Th17/IL-17 was mediated through stimulating lymphocytes in spleen and draining lymph nodes to promote IL-6 production. Epicutaneous sensitization of mice with a combination of Ova and SEB significantly enhanced Ova-induced AHR and granulocytic lung inflammation than Ova allergen alone. When IL-17A was deleted genetically, the effects of SEB on augmenting lung inflammation and AHR were markedly diminished. These findings suggest that chronic heavy colonization of enterotoxin producing S. aureus in the skin of patients with atopic dermatitis may have an important role in the development of atopic march via an IL-17A dependent mechanism.     

Development of atopic dermatitis-like skin lesions in STAT6-deficient NC/Nga mice

Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by elevation of plasma levels of total IgE, infiltration of mast cells and eosinophils, and the expression of cytokines by Th2 T cells. However, the role of Th2 cells in the pathogenesis of AD is not fully understood. In this study we examined the NC/Nga (NC) mouse model of AD and established STAT6-deficient (SATA6(-/-)) NC mice to investigate the relevance of IL-4-mediated immune responses. Surprisingly, these mice elicited AD-like skin lesions at equivalent frequency and time of onset compared with normal NC littermates. Histological features of the lesion in STAT6(-/-) NC mice fulfilled the criteria for the pathogenesis of AD, although these mice fail to produce IgE and Th2 cytokines. The lymph nodes proximal to the regions of skin that developed lesions exhibited massive enlargement elicited by the accumulation of activated IFN-gamma-secreting T cells. Moreover, caspase I, IL-18, IL-12, and IFN-gamma are found to be highly expressed at the skin lesion, occurring simultaneously with elevation of eotaxin 2 and CCR3 expression. Therefore, the Th2-mediated immune response is not necessary for the development of AD-like skin disease in NC mice. The skin microenvironment that favored IFN-gamma production tightly correlates with the skin disease in NC mice through the infiltration of eosinophils.     

Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis

Atopic dermatitis (AD) is a refractory and recurrent inflammatory skin disease. Various factors including heredity, environmental agent, innate and acquired immunity, and skin barrier function participate in the pathogenesis of AD. T -helper (Th) 2-dominant immunological milieu has been suggested in the acute phase of AD. Antigen 85B (Ag85B) is a 30-kDa secretory protein well conserved in Mycobacterium species. Ag85B has strong Th1-type cytokine inducing activity, and is expected to ameliorate Th2 condition in allergic disease. To perform Ag85B function in vivo, effective and less invasive vaccination method is required. Recently, we have established a novel functional virus vector; recombinant human parainfluenza type 2 virus vector (rhPIV2): highly expressive, replication-deficient, and very low-pathogenic vector. In this study, we investigated the efficacy of rhPIV2 engineered to express Ag85B (rhPIV2/Ag85B) in a mouse AD model induced by repeated oxazolone (OX) challenge. Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. The treated mice showed no clinical symptom of croup or systemic adverse reactions. The respiratory tract epithelium captured rhPIV2 effectively without remarkable cytotoxic effects. These results suggested that rhPIV2/Ag85B might be a potent therapeutic tool to control allergic disorders.