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。     

基于NF-κB信号通路的益生菌治疗溃疡性结肠炎的研究进展

溃疡性结肠炎（UC）是一种肠道非特异性炎症性疾病,迁延不愈,严重影响患者的生活质量。目前认为,肠道菌群的改变是诱发和维持结肠炎症的主要原因。临床上应用益生菌制剂作为UC患者的辅助治疗,可平衡患者肠道菌群,减轻炎症反应。UC患者免疫调节功能紊乱,TLR4及其信号传导通路是UC发病的重要环节。易感人群肠道中的菌群突破肠上皮屏障,免疫系统被各种微生物抗原激活,炎症细胞活化从而导致结肠黏膜组织产生炎症反应,该过程可由TLR4-NF-κB信号传导通路介导。本研究就益生菌基于TLR4-NF-κB信号通路对溃疡性结肠炎的治疗进行综述。     

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。     

溃疡性结肠炎缓解期服用益生菌制剂维持治疗的Meta分析

目的系统评价益生菌制剂用于溃疡性结肠炎(ulcerative colitis,UC)缓解期维持治疗的疗效。方法采用计算机检索和手工检索两种方法,以益生菌及其近义词、溃疡性结肠炎等主题词检索Cochrane国际协作网随机对照试验(RCT)注册数据库、PubMed、Embase数据库和中国期刊网等数据库(1978-2009),所选文献符合缓解期UC的诊断标准,以美沙拉嗪为对照的随机对照试验。采用Cochrane系统评价员手册4.2.2推荐的方法纳入文献,并对其进行Meta分析。结果共纳入6个RCT,包括629名患者,Meta分析结果显示:临床复发率益生菌组与美沙拉嗪差异无显著性(OR=0.84,95%CI:0.59~1.19,P=0.33)。结论益生菌制剂与美沙拉嗪对于UC缓解期维持治疗的疗效相近,益生菌制剂是有效的溃疡性结肠炎缓解期维持治疗药物。     

益生菌制剂对2型糖尿病患者的疗效及其对其肠道菌群的影响

目的 探讨益生菌制剂对2型糖尿病患者的疗效及其对肠道菌群的影响。 方法 选取医院收治的92例2型糖尿病患者随机分为对照组和研究组,各46例。对照组给予基础治疗,研究组给予基础治疗联合益生菌制剂。对比治疗前后两组患者临床症状评分和糖代谢指标水平变化,肠道菌群的组成及多样性变化,治疗效果和药物不良反应。 结果 治疗后两组患者Chao1指数和Shannon指数均升高(均P0.05)。 结论 益生菌制剂能够控制2型糖尿病患者的临床症状,改善糖代谢,增加肠道菌群的多样性,调节肠道菌群属水平相对丰度,还可增强疗效且安全。     

功能性便秘的微生态学的防治策略

功能性便秘是儿童时期常见的消化系统功能性疾病,其主要特点为经常排便困难和疼痛,可伴有大便失禁和(或)腹痛。其不仅影响患儿的生活质量,还给患儿带来严重的心理及精神负担。其具体发病机制尚不完全清楚,临床常采用综合治疗方法,但一部分患儿治疗效果欠佳。近年来随着对肠道微生态学的研究逐渐增多,了解到肠道菌群失调与便秘的发生有重要关联,人们也在开始尝试将益生菌等微生态制剂应用于功能性便秘患儿,但其治疗效果有待进一步证实。本文主要通过收集有关功能性便秘患儿应用益生菌及益生元等制剂后的效果,分析益生菌等微生态制剂在治疗功能性便秘患儿的效果,以指导未来临床对功能性便秘患儿的治疗。     

昆明市儿童医院治疗腹泻用药品种分析

目的分析小儿腹泻用药品种,为临床用药、药品购进提供参考。方法统计昆明市儿童医院１９９６年８月至１９９８年８月西药库帐目统计、药品消耗之品种,分两年进行比较分析,按各品种消耗量多少排列顺序。结果１９９６年８月至１９９７年８月为：乳酶片,多酶片,古胺卡那,思密达,乳酸菌素,先锋铋,小儿痢宝,回春生,妈噗爱,培菲康,米雅。１９９７年９月至１９９８年８月为：乳酸菌素,促菌生,妈咪爱,回春生,先锋铋,思密达,乳酶生,多酶,丁胺卡那,培菲康,米雅。两年的比较显示：微生态调节剂的应用有明显上升趋势,尤其益生菌制剂更为突出居上。讨论随着肠道微生态的深入认识和微生态制剂的临术应用,对小儿腹泻的治疗以基于益生菌种有害菌的认识,重视到肠道菌群平衡的问题。小儿一方面由于免疫系统还不成熟,机体很容易感染各种疾病,另一方面由于采用抗生素治疗,使正常菌群发生改变,生态失调,引起菌群交替症,导致腹泻。因此使用微生态制剂治疗,使之肠道内保持一个安定的生态平衡的正常肠内菌群,对于包括各种病原菌在内的外籍菌引起的肠道感染具有明显的抵抗力就格外显得重要。结论临床应用微生态调节剂取得良好疗效,尤其益生菌活菌制剂的应用,为小儿腹泻拓宽了一条新路     

益生菌的治疗现状与前景以及 对呼吸道有益菌探索的研究进展

益生菌是调节机体微生态失衡的有效途径。肝功能异常影响肠道微生物,慢性肝衰竭、2型糖尿病、动脉粥样硬化相关心血管疾病等与肠道微生态失衡密切相关。同时肠道菌群亦受环境、遗传等复合条件影响,改变菌群组成可能导致疾病的发生发展。提倡益生菌对疾病的预防、治疗、预后,改善机体微环境,提高生命质量。近年来,益生菌、益生元、合生元三方面的研究飞速发展,对肠道益生菌研发已经取得一定成果。呼吸道作为与外界相通的腔道其优势菌群已经有相关报道,但对呼吸道益生菌的探索尚不明确,呼吸道内的优势菌是否可以制成益生菌制剂尚有待研究。     

循环水养殖系统中凡纳滨对虾肠道微生物对三种复合益生菌制剂的响应

【目的】在循环养殖系统中应用不同的复合益生菌制剂,探讨凡纳滨对虾肠道菌群结构特征及免疫水平发生的变化。【方法】30 d养殖周期结束后,通过平板计数法分析肠道细菌总数和弧菌总数;基于高通量测序技术分析肠道样品V3+V4区菌群特征;采用实时荧光定量PCR技术分析免疫相关因子TLR1和Dorsal基因表达水平,阐述益生菌制剂应用的意义。【结果】益生菌制剂的应用降低了凡纳滨对虾肠道中细菌总数,抑制弧菌的生长,间接预防疾病的发生。不同益生菌制剂从不同程度上优化了凡纳滨对虾肠道菌群结构,提高高质量序列和有效OTU数量,Chao1、Simpson、Shannon指数显示了丰富度和多样性变化,复合益生菌制剂3效果较好。同时,菌群结构得到优化,其中益生菌制剂1组对拟杆菌门含量百分比产生显著影响。Toll受体TLR1和Toll通路中的Dorsal基因m RNA表达受到益生菌制剂的影响,1、3组促进了TLR 1表达,1、2、3组都促进了Dorsal基因表达。【结论】在循环水养殖系统中添加益生菌制剂可优化凡纳滨对虾肠道菌群特征,提高免疫水平,为病害防控和健康养殖提供理论依据。     

溃疡性结肠炎患者肠道菌群分布的研究现状

溃疡性结肠炎(Ulcerative colitis,UC)的发病被认为是宿主遗传易感性、黏膜免疫与肠道菌群共同作用的结果。许多临床研究显示,与正常人相比,UC患者存在不同程度的菌群失调。艰难梭菌、致病性大肠埃希菌等致病微生物被怀疑与UC的发病相关,但目前还未找到充分证据证明它们与UC患者肠道炎症间的因果关系。就UC患者肠道菌群分布的研究现状、肠道菌群检测方法及未来研究进展进行了阐述。     

粪菌移植治疗溃疡性结肠炎的临床应用前景探讨

溃疡性结肠炎(UC)是一种炎症性肠病(IBD), 其病因尚不清楚, 以慢性、反复复发、迁延不愈为特征, 临床治疗效果欠佳。UC的病因和发病机制包括环境、遗传、微生物和免疫等因素, 这些因素相互作用, 增加肠上皮细胞通透性, 最终导致过度的免疫反应。粪菌移植(FMT)作为一种重塑肠道菌群的治疗方法, 可帮助肠道菌群失调的UC患者重建肠道新的肠道微生态。本文从肠道微生态角度出发, 阐述FMT、肠道微生态和UC之间的联系, 探讨目前FMT治疗UC的可能机制。

     

P2RY13 Exacerbates Intestinal Inflammation by Damaging the Intestinal Mucosal Barrier via Activating IL-6/STAT3 Pathway

The pathogenesis of ulcerative colitis (UC) is unclear, while genetic factors have been confirmed to play an important role in its development. P2RY13 is a G protein-coupled receptor (GPCRs), which are involved in the pathogenesis of inflammation and immune disorders. According to GEO database analysis, we first observed that the expression of P2Y13 was increased in UC patients. Therefore, we sought to determine the role of P2Y13 in the development of colitis. Our data showed that P2RY13 was highly expressed in the inflamed intestinal tissues of UC patients. In mice, pharmacological antagonism of P2Y13 can significantly attenuate the intestinal mucosal barrier disruption. In LPS-induced NCM460 cell, knockdown or pharmacological inhibition of P2RY13 increased the expression of intestinal tight junction protein and reduced apoptosis. In addition, we found that the effect of P2Y13 on colitis is related to the activation of the IL-6/STAT3 pathway. Activation of P2Y13 increases IL-6 expression and promotes STAT3 phosphorylation and nuclear transport. Deletion of the STAT3 gene in the intestinal epithelial cells of mice significantly mitigated the exacerbation of colitis due to P2Y13 activation. Thus, P2Y13 can aggravate intestinal mucosal barrier destruction by activating the IL-6/STAT3 pathway. P2Y13 might be a potential drug target for UC.     

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.     

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。     

不同发病时期溃疡性结肠炎患者肠道菌群差异及对血清TLRs/NFκB和SOCS3 及Cingulin蛋白水平的影响

目的 分析溃疡性结肠炎(UC)患者不同发病时期肠道菌群的差异,同时研究菌群变化及对患者血清TLRs/NFκB、SOCS3、Cingulin蛋白水平的影响。 方法 选取2015年5月至2017年2月在我院确诊的UC患者为研究对象。将活动性溃疡性结肠炎(AUC)患者和缓解性溃疡性结肠炎(RUC)患者按病情不同分为AUC组(48例)和RUC组(42例)。选取同期在我院发现的结肠息肉患者作为对照组(50例)。对3组患者的肠道菌群分布、Cingulin蛋白表达量、肠黏膜中TLRs/NFκB的表达量和外周血中SOCS3及TNFα水平进行对比。 结果 UC患者(AUC组及RUC组)肠道大肠埃希菌数量高于对照组,双歧杆菌数量低于对照组;同时RUC组患者肠道乳杆菌数量低于对照组,差异均有统计学意义(均P结论 TNFα、SOCS3可能参与UC的病程,其在UC患者中存在高表达现象,可导致人体肠道菌群出现紊乱,最终引发人体多部位的炎症应激反应。     

Protein-tyrosine phosphatase sigma is associated with ulcerative colitis

Inflammatory bowel disease (IBD), a relatively common chronic debilitating intestinal illness, is composed of two broadly defined groups, Crohn's disease (CD) and ulcerative colitis (UC). Although several susceptibility genes for CD have been recently described, susceptibility genes exclusive for UC have not been forthcoming. Here, we show that receptor protein-tyrosine phosphatase sigma (PTPRS-encoding PTPsigma) knockout mice spontaneously develop mild colitis that becomes severe when challenged with two known inducers of colitis. We also demonstrate that E-cadherin and beta-catenin, two important adherens junction proteins involved in maintenance of barrier defense in the colon, act as colonic substrates for PTPsigma. Furthermore, we show that three SNPs (rs886936, rs17130, and rs8100586) that flank exon 8 in the human PTPRS gene are associated with UC. The presence of these SNPs is associated with novel splicing that removes the third immunoglobulin-like domain (exon 9) from the extracellular portion of PTPsigma, possibly altering dimerization or ligand recognition. We propose that polymorphisms in the human PTPRS gene lead to ulcerative colitis.     

Epithelial PBLD attenuates intestinal inflammatory response and improves intestinal barrier function by inhibiting NF-κB signaling

Intestinal barrier function defects and dysregulation of intestinal immune responses are two key contributory factors in the pathogenesis of ulcerative colitis (UC). Phenazine biosynthesis-like domain-containing protein (PBLD) was recently identified as a tumor suppressor in gastric cancer, hepatocellular carcinoma, and breast cancer; however, its role in UC remains unclear. Therefore, we analyzed colonic tissue samples from patients with UC and constructed specific intestinal epithelial PBLD-deficient (PBLD^IEC−/−) mice to investigate the role of this protein in UC pathogenesis. We found that epithelial PBLD was decreased in patients with UC and was correlated with levels of tight junction (TJ) and inflammatory proteins. PBLD^IEC−/− mice were more susceptible to dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid-induced colitis compared with wild-type (WT) mice. In DSS-induced colitis, PBLD^IEC−/− mice had impaired intestinal barrier function and greater immune cell infiltration in colonic tissue than WT mice. Furthermore, TJ proteins were markedly reduced in PBLD^IEC−/− mice compared with WT mice with colitis. Nuclear factor (NF)-κB activation was markedly elevated and resulted in higher expression levels of downstream effectors (C–C motif chemokine ligand 20, interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α) in colonic epithelial cells isolated from PBLD^IEC−/− mice than WT mice with colitis. PBLD overexpression in intestinal epithelial cells (IECs) consistently inhibited TNF-α/interferon-γ-induced intestinal barrier disruption and TNF-α-induced inflammatory responses via the suppression of NF-κB. In addition, IKK inhibition (IKK-16) rescued excessive inflammatory responses induced by TNF-α in PBLD knockdown FHC cells. Co-immunoprecipitation assays showed that PBLD may interact with IKKα and IKKβ, thus inhibiting NF-κB signaling, decreasing inflammatory mediator production, attenuating colonic inflammation, and improving intestinal barrier function. Modulating PBLD expression may provide a novel approach for treatment in patients with UC.Subject terms: Ulcerative colitis, Chronic inflammation