益生菌治疗反复呼吸道感染的相关机制

反复呼吸道感染是儿童常见的慢性呼吸道疾病,发病机制复杂,病因及治疗方法较多.益生菌是近年来临床应用较多的免疫调节剂之一,本文综述了反复呼吸道感染患儿肠道菌群的变化,并从调节肠道菌群、增强肠黏膜屏障、刺激肠道黏膜生长、调节机体免疫等方面阐述了益生菌治疗反复呼吸道感染的相关机制.     

肠道菌群与儿科肠道炎症性疾病研究进展

新生儿坏死性小肠结肠炎(NEC)、儿童炎症性肠病(IBD)及先天性巨结肠合并小肠结肠炎(HAEC)等是儿科较常见的、严重影响患儿生活质量甚至威胁生命的肠道炎症性疾病。目前其发病机制尚不明确。研究表明,肠道炎症性疾病与肠道菌群紊乱有密切关系,但约85%的肠道细菌无法由培养得到。近年来高通量测序技术的迅速发展,使全面深入探究肠道微生物群落成为可能。文章综述近年来肠道菌群在儿科肠道炎症性疾病发病中的作用及益生菌应用的研究进展。     

肠道菌群与儿童过敏性疾病

肠道菌群在调节机体免疫功能、维持肠道黏膜屏障、抑制外源性致病菌定植等方面具有重要作用.近年来流行病学调查和实验研究提示生命早期肠道菌群的紊乱与过敏性疾病的发生发展有密切关系.关于益生菌对过敏性疾病的预防和治疗作用,近年来已有多项研究,但尚无确切结论.     

婴幼儿轮状病毒肠炎肠道菌群的动态变化

对３９例轮状病毒腹泻患儿肠道菌群进行定量检查，与３０名健康儿童对照比较，双歧杆菌、拟杆菌、乳杆菌和肠球菌数量显著下降，肠杆菌在菌群中所占比例相对升高，提示肠菌群失调。对其中２０例腹泻患儿进行肠菌群动态定量分析，发现在发病早期即出现肠菌群紊乱，随着腹泻症状消退，肠菌群失调逐渐纠正，而且厌氧菌上升速度较快。提示菌群失调程度与临床病情及脱水程度有关。     

益生菌对肠黏膜屏障的作用机制

肠黏膜屏障是指正常肠道具有的将肠腔内物质与机体内环境隔离,防御外来抗原及致病性病原体侵入黏膜下层组织的功能,维持机体内环境的相对稳定和机体的正常生命活动.肠黏膜屏障功能的损伤与多种胃肠道疾病的发生密切相关.益生菌是指摄取后在肠道达到一定数量能够对宿主起有益作用的活微生物,它能够改善或预防多种胃肠道疾病,其主要机制为益生菌能够通过多种途径维持肠黏膜屏障功能.该文就益生菌对肠黏膜屏障功能的具体作用机制作一综述.     

粪菌移植在儿科应用的研究进展北大核心CSCD

粪菌移植(FMT)可将健康人粪便中的各种肠道微生物、代谢产物和天然抗菌物质等移植到受者肠道内,可重建肠道菌群平衡、修复肠黏膜屏障、控制炎症反应、调节机体免疫,是治疗肠道菌群失调所致疾病的新方法。FMT治疗儿童复发性艰难梭菌感染已写入复发性艰难梭菌感染的诊疗指南。FMT治疗儿童炎症性肠病、孤独症谱系障碍的有效性及安全性较好。     

益生菌治疗孤独症谱系障碍的展望

孤独症谱系障碍(ASD)是一种严重的发育障碍性疾病,至今以康复教育治疗为主。近年来研究发现,ASD儿童常伴有胃肠道症状,可能与菌群失衡和微生物-肠-脑轴有关。动物实验和临床观察表明,肠道菌群失衡可以导致ASD肠上皮细胞损害、黏膜免疫和神经递质等发生改变,出现一系列胃肠道症状和异常行为,而用益生菌治疗ASD既可缓解其胃肠道症状,也可改善部分行为问题。虽然尚需要更严谨的临床和基础实验对益生菌治疗ASD的疗效、机制等展开研究,但可以认为,益生菌在治疗ASD上有值得期待的潜在作用。     

益生菌在儿童炎症性肠病的应用

炎症性肠病(inflammatory bowel disease,IBD)是一组病因未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)和克罗恩病(Crohn’s disease,CD)。随着人们对肠道微生物在IBD发病中认识的加深,益生菌在儿童IBD治疗中显示出良好的前景,但目前仍缺乏高质量证据确证益生菌菌株疗效,指导临床对益生菌菌种、摄入方式、剂量等进行选择。现有研究表明,益生菌发挥治疗作用存在菌株特异性,且在诱导UC缓解、维持UC缓解以及预防贮袋炎方面的效果更为明显,但益生菌诱导CD、维持CD缓解和预防CD术后复发的效果并不理想。     

关注微生态制剂在儿童中的应用

随着肠道菌群与人类健康和疾病关系研究的深入,微生态制剂越来越受到儿科医务人员和公众的关注,微生态制剂包括益生菌、益生元、合生元和后生元,其中益生菌是目前应用最为广泛的制剂。益生菌能够通过拮抗潜在致病菌、增强黏膜免疫功能和肠道屏障功能、激活和调节全身免疫应答、改善肠道代谢等,发挥对某些疾病的防治和健康促进作用。益生菌可以以药物、配方奶添加、食品添加和保健品等方式补充。益生菌具有菌株特异性、剂量依赖性和个体或人群差异性的特点,是临床进行益生菌应用选择、推荐和评价的主要依据。     

肠肺轴——谁影响谁

人体肠道是一个巨大的微生物栖息地, 肠道菌群为人体提供营养、调节代谢、调控肠道上皮发育和诱导先天性免疫, 对生长、发育、衰老有着重要的影响。肠道菌群受遗传因素、生活环境或生活模式以及疾病等多种因素的影响, 同时也通过多种途径与全身脏器相互影响。肺与大肠具有胚胎学同源性、共同黏膜免疫系统、具有分泌功能等现代生物学基础, 肠道菌群既调节胃肠道的功能, 也影响呼吸系统健康与疾病, 形成"肠肺轴";依据肠肺轴理论, 肠道微生态调控已在预防和治疗呼吸道感染、哮喘等多种呼吸系统疾病取得较好疗效。     

Very early onset inflammatory bowel disease

Very early onset inflammatory bowel disease (VEO-IBD) represents a unique and growing subset of patients with inflammatory bowel disease (IBD). Some VEO-IBD patients present with immunodeficiency and possess loss of function genetic mutations involving immune pathways that cause their IBD. A search for Mendelian causes of IBD is likely most beneficial when the presentation involves extra-intestinal autoimmunity or involves intestinal histopathology that is atypical for IBD. While a subset of these young patients will have highly aggressive courses (and likely present with immunodeficiency), the majority of patients with VEO-IBD appear to have disease courses similar to that of their older counterparts. Most notably, many of these young children will require long courses of immunosuppression simply as a result of the profoundly early presentation—thus increasing their long-term risks of cancer and opportunistic infections.     

Th17/Treg平衡在炎症性肠病中的意义

炎症性肠病为一类慢性非特异性肠道炎性疾病,肠道黏膜免疫系统异常反应在炎症性肠病发病机制中发挥重要作用.辅助性T细胞17(Thelper 17 cell,Th17)可介导慢性炎症和自身免疫性疾病的发生,调节性T细胞(regulatory T cell,Treg)有抑制自身免疫的功能,Th17/Treg细胞平衡是维持肠道免疫稳态的重要因素.抗原提呈细胞、微生物、一些关键分子、天然化合物可以调节Th17/Treg平衡,从而为治疗炎症性肠病提供新的方法.     

Paediatric Inflammatory Bowel Diseases – brief update on current practice and future perspectives

Inflammatory Bowel Diseases (IBD) are chronic disorders of the digestive tract that result in relapsing inflammation of the intestinal mucosa. Over the last few decades we have seen a significant increase in the incidence of these conditions. This increase has been particularly noticeable in children and young adults, who currently contribute almost 30% of all patients diagnosed with IBD. Despite major advances in our knowledge, the exact cause of IBD remains unknown and in the absence of a curative treatment patients are still faced with a lifelong disabling condition. In the following brief review we will summarise current practice in diagnosing and managing children with IBD and highlight some of the recent advances. Additionally, we will briefly discuss ongoing research in the field and introduce epigenetics as a novel concept with a potential to explain some of the missing links in IBD disease pathogenesis.     

谷氨酰胺强化肠内营养对炎症性肠病幼鼠模型结肠黏膜细胞凋亡作用的研究

目的 探讨谷氨酰胺强化肠内营养对炎症性肠病（IBD）幼鼠模型肠黏膜细胞凋亡的调控及促进黏膜愈合的作用。方法 将80只4~5周龄Sprague-Dawley雄性大鼠随机分为空白对照组、IBD模型组、短肽组和短肽+谷氨酰胺（Gln）组,每组20只。采用一次性结肠灌注三硝基苯磺酸建立IBD模型,造模3 d后,短肽组给予短肽制剂（100 mL/kg）,短肽+Gln组给予短肽制剂（100 mL/kg）+Gln（0.5 g/kg）,干预1周。实验结束后观察幼鼠的一般情况,并留取肠黏膜,苏木素-伊红（HE）染色观察肠黏膜组织病理情况;RTPCR法检测肠黏膜凋亡调控基因（bax、bcl-2）及凋亡信号转导因子（Caspase-3、Caspase-9）的表达;Westernblot法检测结肠黏膜IGF-1表达水平。结果 IBD模型组一般情况均较其他组差,短肽+Gln组一般情况优于IBD模型组和短肽组。模型组bax mRNA表达水平高于空白对照组、短肽组和短肽+Gln组（P < 0.05）;bcl-2、Caspase-3、Caspase-9 mRNA水平在各组比较差异均无统计学意义（P > 0.05）。短肽组IGF-1水平明显高于短肽+Gln组、空白对照组及IBD模型组（P < 0.05）。结论 Gln强化肠内营养能有效改善IBD模型幼鼠的一般营养状况,但在抑制结肠黏膜细胞凋亡及刺激结肠黏膜IGF-1合成方面并未优于专一肠内营养。     

Colonoscopy and technetium-99m white cell scan in children with suspected inflammatory bowel disease

OBJECTIVES: To determine the utility of the technetium-labeled autologous white cell scintigraphy (Tc-WCS) for detecting intestinal inflammation in children with suspected inflammatory bowel disease (IBD). Tc-WCS was compared with colonoscopy and histologic examination. STUDY DESIGN: Forty-eight children (26 boys; median age, 10 years; range, 2-17 years) with symptoms and signs suggesting IBD had colonoscopy with exploration of terminal ileum and mucosal biopsies. The scans were judged to be abnormal if activity was seen in the gut within the first hour. RESULTS: Twenty-one patients had a diagnosis of IBD (Crohn's disease, 13; ulcerative colitis, 5; indeterminate colitis, 3); results of scintigraphy were positive in 16 and negative in 5 (sensitivity, 76.2%); the latter had a moderate degree of intestinal inflammation. In 27 patients, IBD was ruled out. Results of scintigraphy were negative in children with non-specific colitis and in those with lymphoid hyperplasia of the terminal ileum, whereas results were positive in 6 of 12 patients with spondyloarthropathy. In children with IBD, there was a significant correlation between results of scintigraphy and endoscopy for the intensity of inflammation (r = 0.70); however, there was a poor correlation regarding the number of involved segments (r = 0.30) because in 16 patients, endoscopy revealed additional diseased segments as compared with scintigraphy. CONCLUSIONS: A positive Tc-WCS result indicates the presence of an inflammatory process of the gut, whereas a negative test result does not rule out intestinal inflammation, especially when the latter is of moderate degree. Colonoscopy and biopsy are the investigations of choice to establish the diagnosis of IBD and are superior to Tc-WCS in assessing topographic extension of IBD.     

Overview of paediatric IBD

Inflammatory bowel disease (IBD) is a chronic complex disease of children and adults requiring a range of medications and surgical techniques to induce and maintain remission. In common with other immune-mediated inflammatory disorders, it has shown an ever-increasing rise in incidence worldwide over the last 50 years. The cause of IBD arises from interactions between the microbiome in the gut and the gastrointestinal and systemic immune system in genetically susceptible persons, and with environmental triggers to both develop IBD and have relapses of IBD. The burden of IBD in children and adolescents can be high, and treatment needs a multi-disciplinary approach aiming to abolish symptoms, promote growth and development, and support a restriction-free life. Achieving healing of the intestinal mucosa promotes long-term remission and helps to avoid disease complications.     

De novo inflammatory bowel disease after pediatric kidney or liver transplant

A subset of children who receive a liver and/or kidney transplant develop de novo inflammatory bowel disease‐like chronic intestinal inflammation, not explained by infection or medications, following transplant. We have conducted a single‐center, retrospective case series describing the unique clinical and histologic features of this IBD‐like chronic intestinal inflammation following solid organ transplant. At our center, nine of 327 kidney or liver recipients developed de novo IBD following transplant (six liver, two kidney, one liver‐kidney). Most children presented with prolonged hematochezia and diarrhea and were treated with aminosalicylates. At time of diagnosis, five were not currently using mycophenolate mofetil for transplant immunosuppression. Histologic and endoscopic findings at IBD diagnosis included inflammation, ulcerations, granulomas, and chronic colitis. Since diagnosis, no patients have required surgical intervention, or escalation to biologic therapy, nor developed stricturing or perianal disease. In this case series, de novo post‐transplant IBD developed in 4% of pediatric liver and/or kidney recipients; however, it often does not fit the classic patterns of Crohn's disease or ulcerative colitis.     

Colonic expression of MUC2, MUC5AC, and TFF1 in inflammatory bowel disease in children

BACKGROUND: The quantity and quality of mucins are affected in inflammatory bowel disease (IBD) both because of a reduction in the number of goblet cells and a decrease in the number of sugar residues per oligosaccharide side chain. Alteration in the types of mucins and aberrant location may contribute to the underlying pathology by affecting the mucus barrier function or may instead be a response to inflammation. The authors used the periodic acid-Schiff/Alcian blue stain to distinguish neutral and acidic mucins, and used specific antibodies to the mature goblet cell mucin MUC2, MUC2 core antigen, foveolar cell mucin MUC5AC, and gastric trefoil factor (TFF1), to characterize their presence and distribution in colonic tissue sections from patients with IBD. RESULTS: Both core and mature MUC2 were expressed in all colonic goblet cells from patients with ulcerative colitis (UC) and Crohn disease and from healthy controls. MUC5AC and TFF1, which are not normally expressed by colonic tissue, also were expressed in scattered goblet cells, coexpressing with MUC2. In areas of goblet cell depletion, MUC2 was present in cytoplasmic granules of flattened, cuboidal, nongoblet-cell-like surface cells. The staining was more intense and homogenous with the MUC2 core antibody, suggesting expression of relatively immature mucin. Some of these cells also coexpressed MUC5AC but to a lesser extent. These findings are not unique to IBD but were also found in other types of intestinal inflammation. CONCLUSION: The study confirms earlier observations that MUC2 is the major colonic mucin in IBD. It appears in two forms: mature MUC2 in goblet cells and immature MUC2 especially in secretory granules of cells that are not phenotypically goblet cells. MUC5AC and TFF1 expression in goblet cells is common in IBD and other inflammatory conditions of the colon. These changes may represent a nonspecific repair function of the colon cells to compensate for damage to barrier function.     

极早发型炎症性肠病的特点与治疗

炎症性肠病（IBD）是一种病因不明的慢性非特异性肠道炎症性疾病。该疾病包括3种主要类型：克罗恩病（CD）、溃疡性结肠炎（UC）和未分型IBD（IBD-U）。IBD在成人中发病率高，但近年来，IBD在儿童中发病率越来越高。极早发型IBD（VEO-IBD）是儿童IBD的一部分，有其独特的表型和遗传学特征，通常病情严重，并且对常规IBD治疗效果差。该文对VEO-IBD的临床特点、发病机制和治疗进行了综述。     

儿童炎症性肠病与免疫缺陷

炎症性肠病（IBD）是指原因不明的一组慢性非特异性、 反复发作的肠道炎症性疾病。儿童IBD的发病率在过去的50年里明显增高。一般将发病年龄＜6岁的IBD称为极早发IBD（VEO-IBD）,占儿童IBD的4%～10%。VEO-IBD被认为与遗传因素相关性更大,单基因突变检出率更高。该部分具有单基因突变的VEO-IBD,其受累基因很多归为原发性免疫缺陷病。这些基因缺陷导致固有免疫、适应性免疫、上皮屏障等多方面功能损伤,从而导致VEO-IBD的发生。由于不同类型原发性免疫缺陷病合并IBD的治疗手段及预后有所不同,可通过基因测序技术实现早期诊断,选择合适的治疗方法,从而实现早期干预,改善患者的预后。