肠道菌群与1型糖尿病免疫机制的研究进展

1型糖尿病是一种T细胞介导的好发于青少年的自身免疫性疾病, 以胰岛β细胞进行性破坏、胰岛素绝对缺乏、高血糖为主要特征。1型糖尿病的发病机制较为复杂, 目前认为其主要与免疫、环境、遗传有关。越来越多的证据表明, 肠道菌群与1型糖尿病的发生密切相关。本文从固有免疫和适应性免疫角度, 重点探讨了肠道菌群及其衍生物在1型糖尿病发生发展中的相关免疫机制和作用, 并介绍了以肠道菌群为靶点治疗1型糖尿病的方法。     

肠道病毒感染在家庭内部传播导致1型糖尿病发生

1型糖尿病是一种具有遗传基础、由环境因素诱发的器官特异性自身免疫性疾病。近年的研究显示环境因素中的肠道菌群的改变及病毒感染可能在糖尿病发病中扮演重要作用。而肠病毒（EVs）的感染可能与1型糖尿病的早期临床阶段有关。血液中EVs的出现可能作为1型糖尿病的生物学标志物。     

基于肠道菌群与肠道免疫相互作用认识溃疡性结肠炎发病的研究概况

溃疡性结肠炎是临床常见的消化系统炎症性疾病,由于该病的发病率逐年增加,且易并发胃肠道急重症,逐渐引起了医患重视。其发病机制是多因素的,涉及遗传易感性、环境因素、微生物生态失调和免疫应答失调,然而单一因素却难以解释该病症状的异质性和复杂性。研究发现肠道菌群与宿主肠道免疫系统的相互作用使得该病表现出症状的异质性。故基于肠道菌群与肠黏膜免疫的相互作用探索该病发病以期深刻认识该病从而探索高效的干预方式。     

肠道菌群在食物过敏发生和发展中的作用机制

食物过敏是一种由食物变应原引起的异常免疫反应。食物过敏的发生和发展是遗传因素与环境因素的共同作用,其中环境因素发挥重要作用,但其发病机制尚不明确。多项研究表明,肠道菌群与食物过敏的发生和发展密切相关,肠道菌群失衡可通过增强Th2型免疫应答,干扰免疫成熟,减少Treg细胞,破坏肠道黏膜屏障等机制导致机体出现食物过敏。本文针对肠道菌群紊乱与食物过敏的关系及其潜在机制进行综述,为食物过敏的早期预防及病因治疗提供依据。     

肠道菌群与肥胖和2型糖尿病的相关性

近年来研究发现肠道菌群、肥胖、胰岛素抵抗及2型糖尿病之间有着紧密的联系.有证据表明,在宿主的营养、免疫和代谢中有不可替代的作用的肠道菌群不仅可以通过调节宿主脂肪吸收存储相关的基因,影响后者的能量平衡,更重要的是其结构失调导致宿主循环系统中内毒素增加,诱发慢性、低水平炎症,导致肥胖和胰岛素抵抗及糖尿病.肠道菌群影响人体健康已得到初步证明,研究结果表明肠道菌群很可能与肥胖及2型糖尿病的发生发展有密切联系[1],但是究竟是如何联系的呢？我们对此进行如下综述.     

心肠对话:肠道菌群在心血管疾病中的作用

心血管疾病(CVD)是对人类健康构成极大威胁的一类疾病,其发生、发展往往受遗传与环境的多种因素影响。肠道菌群是人体内数目最大的菌群库,影响宿主的生理代谢,近年来肠道菌群与宿主间的相互作用逐渐受到重视。肠道微生物群在人类健康和疾病中发挥着重要作用,许多研究证实了肠道菌群及其代谢产物可从血脂异常、2型糖尿病、高血压、动脉粥样硬化、心力衰竭等多个方面影响CVD。因此,以肠道菌群作为CVD治疗靶点的方案值得探索。本文将对肠道菌群在CVD发病机制中的作用及通过调节肠道菌群治疗CVD的方法进行系统综述。     

肠道菌群与肥胖和糖尿病的关系

人的胃肠道内寄居着种类繁多的单细胞微生物,称为肠道菌群.基因、出生方式、婴幼儿喂养模式、抗生素应用、卫生居住条件以及长期的饮食习惯有助于塑造肠道菌群的组成.越来越多的动物和人体研究表明肠道菌群与肥胖和2型糖尿病密切相关.肠道菌群可通过宿主能量代谢、免疫系统及炎性反应等影响代谢综合征及2型糖尿病的发生、发展.干预肠道菌群有可能成为防治肥胖及糖尿病的新靶点.     

肠道微生态改变在炎症性肠病中的作用

炎症性肠病（IBD）主要包括溃疡性结肠炎（UC）和克罗恩病（CD），其病因和发病机制尚未明确。目前认为IBD的病因为肠道微环境（肠道菌群）、宿主遗传易感性和黏膜免疫因素三者间的相互作用。近年来．随着微生态学的发展，肠道菌群与IBD发病的关系日益受到关注。本文就IBD时肠道菌群的变化、肠道微生态改变对IBD的影响以及微生态制剂对IBD的治疗作用作一综述。     

肠道菌群与2型糖尿病

研究表明,2型糖尿病患者肠道菌群结构及功能与健康人不同,肠道菌群可能通过干预宿主营养及能量的吸收利用,促进脂肪的合成及存储,引发慢性低度炎性反应等机制影响2型糖尿病的发展.多项针对肠道菌群的治疗措施在2型糖尿病的动物模型和人群研究中开展,表明饮食、运动及药物均可通过干预肠道菌群的结构及功能影响糖尿病的发生和发展.干预肠道菌群可能成为今后糖尿病防治领域的重要手段之一.     

肠道菌群失调与动脉粥样硬化相关心血管疾病

肠道菌群失调对动脉粥样硬化相关心血管疾病有重要影响。心血管疾病的诸多危险因素,如高脂血症、肥胖、2型糖尿病和高血压均与肠道菌群失调密切相关,同时肠道菌群还可通过与环境因素和遗传因素的交互作用而间接影响动脉粥样硬化疾病的进展。因此,纠正肠道菌群失调可能作为治疗心血管疾病的新策略。     

临床研究的体会

黎介寿院士从医数十年,见证了中国外科的成长,并在临床工作和研究中为医疗事业进步作出了众多重要的贡献。本文中,笔者结合自己的从医以来在"肠功能障碍"、"快速康复外科"、"小肠移植"等诸多方向上令人瞩目的研究经历,深刻的探讨了医疗研究中发现和解决问题的态度和方法,对广大医生的临床实践有着重要的指导意义。     

Combination of Adult Intussusception and Intestinal Malrotation: An Unusual Presentation

Intussusception is familiar to pediatric surgeons but is rarely encountered by general surgeons. Adult intussusception is uncommon, accounting for less than 5% of intestinal obstructions, half of which are associated neoplasms. Intestinal malrotation is usually an incidental finding with unrelated disease on image studies, laparotomy or even autopsy. The major complications of intestinal malrotation are intestinal obstruction secondary to midgut volvulus, internal hernia, or adhesion band. The association of the two entities, which is named Waugh’s syndrome in infants, has rarely been reported in the literature. The association in adults is even rarer. We report an adult case with an unusual combination of malrotation and intussusception at exploration.     

Phasic study of intestinal homeostasis disruption in experimental intestinal obstruction

AIM: To investigate the phasic alteration of intestinal homeostasis in an experimental model of intestinal obstruction.METHODS: A rabbit model of intestinal obstruction was established by transforming parts of an infusion set into an in vivo pulled-type locking clamp and creating a uniform controllable loop obstruction in the mesenteric non-avascular zone 8 cm from the distal end of the ileum. The phasic alteration of intestinal homeostasis was studied after intestinal obstruction. The changes in goblet cells, intraepithelial lymphocytes, lamina propria lymphocytes, and intestinal epithelium were quantified from periodic acid-Schiff-stained sections. Ornithine decarboxylase (ODC) activity and serum citrulline levels were measured by high-performance liquid chromatography. Claudin 1 mRNA expression was examined by real-time polymerase chain reaction analysis. Intestinal microorganisms, wet/dry weight ratios, pH values, and endotoxin levels were determined at multiple points after intestinal obstruction. Furthermore, the number and ratio of CD3⁺, CD4⁺ and CD8⁺ T cells were determined by flow cytometry, and secretory IgA levels were measured with an enzyme-linked immunosorbent assay.RESULTS: A suitable controllable rabbit model of intestinal obstruction was established. Intestinal obstruction induced goblet cell damage and reduced cell number. Further indicators of epithelial cell damage were observed as reduced serum citrulline levels and claudin 1 gene expression, and a transient increase in ODC activity. In addition, the wet/dry weight ratio and pH of the intestinal lumen were also dramatically altered. The ratio of Bacillus bifidus and enterobacteria was reversed following intestinal obstruction. The number and area of Peyer’s patches first increased then sharply decreased after the intestinal obstruction, along with an alteration in the ratio of CD4/CD8⁺ T cells, driven by an increase in CD3⁺ and CD8⁺ T cells and a decrease in CD4⁺ T cells. The number of lamina propria lymphocytes also gradually decreased with prolonged obstruction.CONCLUSION: Intestinal obstruction can induce disruption of intestinal homeostasis.     

Distribution of bleeding gastrointestinal angioectasias in a Western population

AIM: To define which segments of the gastrointestinal tract are most likely to yield angioectasias for ablative therapy.METHODS: A retrospective chart review was performed for patients treated in the Louisiana State University Health Sciences Center Gastroenterology clinics between the dates of July 1, 2007 and October 1, 2010. The selection of cases for review was initiated by use of our electronic medical record to identify all patients with a diagnosis of angioectasia, angiodysplasia, or arteriovenous malformation. Of these cases, chart reviews identified patients who had a complete evaluation of their gastrointestinal tract as defined by at least one upper endoscopy, colonoscopy and small bowel capsule endoscopy within the past three years. Patients without evidence of overt gastrointestinal bleeding or iron deficiency anemia associated with intestinal angioectasias were classified as asymptomatic and excluded from this analysis. Thirty-five patients with confirmed, bleeding intestinal angioectasias who had undergone complete endoscopic evaluation of the gastrointestinal tract were included in the final analysis.RESULTS: A total of 127 cases were reviewed. Sixty-six were excluded during subsequent screening due to lack of complete small bowel evaluation and/or lack of documentation of overt bleeding or iron deficiency anemia. The 61 remaining cases were carefully examined with independent review of endoscopic images as well as complete capsule endoscopy videos. This analysis excluded 26 additional cases due to insufficient records/images for review, incomplete capsule examination, poor capsule visualization or lack of confirmation of typical angioectasias by the principal investigator on independent review. Thirty-five cases met criteria for final analysis. All study patients were age 50 years or older and 13 patients (37.1%) had chronic kidney disease stage 3 or higher. Twenty of 35 patients were taking aspirin (81 mg or 325 mg), clopidogrel, and/or warfarin, with 8/20 on combination therapy. The number and location of angioectasis was documented for each case. Lesions were then classified into the following segments of the gastrointestinal tract: esophagus, stomach, duodenum, jejunum, ileum, right colon and left colon. The location of lesions within the small bowel observed by capsule endoscopy was generally defined by percentage of total small bowel transit time with times of 0%-9%, 10%-39%, and 40%-100% corresponding to the duodenum, jejunum and ileum, respectively. Independent review of complete capsule studies allowed for deviation from this guideline if capsule passage was delayed in one or more segments. In addition, the location and number of angioectasias observed in the small bowel was further modified or confirmed by subsequent device-assisted enteroscopy (DAE) performed in the 83% of cases. In our study population, angioectasias were most commonly found in the jejunum (80%) followed by the duodenum (51%), stomach (22.8%), and right colon (11.4%). Only two patients were found to have angioectasias in the ileum (5.7%). Twenty-one patients (60%) had angioectasias in more than one location.CONCLUSION: Patients being considered for endoscopic ablation of symptomatic angioectasias should undergo push enteroscopy or anterograde DAE and re-inspection of the right colon.     

隐源性多灶性溃疡性狭窄性小肠炎

隐源性多灶性溃疡性狭窄性小肠炎(CMUSE)是一种以小肠多部位狭窄和多灶性浅溃疡为特点的小肠疾病,主要的临床表现为慢性或复发性肠梗阻。溃疡一般较浅,位于黏膜层和黏膜下层。纤维性狭窄部位较短(一般1~2 cm),相互间隔较紧凑(多为2~10 cm),无瘘管形成。外科手术治疗后复发率高,糖皮质激素可有效防止再次手术,多数患者成为激素依赖状态。     

Safety and efficacy of home parenteral nutrition for chronic intestinal failure: a 16-year experience at a single centre

BACKGROUND: Comparisons between safety and efficacy of home parenteral nutrition and of intestinal transplantation for treatment of chronic intestinal failure derived from observational studies. AIMS: To present the 16-year experience of home parenteral nutrition by the Chronic Intestinal Failure Centre of Bologna University. PATIENTS: A total of 40 adult patients were enrolled between 1986 and 2001. METHODS: Safety indices: survival and cause of death, catheter-related bloodstream infection, deep vein thrombosis, liver disease. Efficacy indices: nutritional and rehabilitation status, quality of life (SF36 instrument), re-hospitalisation rate. Statistics: Kaplan-Maier analysis and Cox model for survival probability and risk factors; logistic regression for catheter-related bloodstream infection risk factors. RESULTS: Survival rates at 1, 3 and 5 years were 97, 82 and 67% respectively. Survival was higher in patients < or = 40 years. One death was home parenteral nutrition-related. Incidence of catheter-related bloodstream infection: 0.30/year home parenteral nutrition, was lower in patients treated by a specialized nursing protocol. Incidence of deep vein thrombosis was 0.05/year home parenteral nutrition. Hepatosteatosis occurred in 55%. Body weight remained stable or increased in 80%. Rehabilitation was total or partial in 74%. Re-hospitalisation rate was 0.70/year home parenteral nutrition. Quality of life scored significantly lower than in healthy populations in six out of eight domains. CONCLUSIONS: Home parenteral nutrition is a safe and efficacious therapy for chronic intestinal failure. Survival compares favourably with survival after intestinal transplantation.     

老年人粪性结肠梗阻与穿孔诊治的体会

目的 分析老年人粪性结肠梗阻与穿孔的临床特征，以提高诊治水平。方法 对1994年1月至2003年12月收治的22例老年粪性结肠梗阻与6例粪性结肠穿孔患者资料进行回顾性分析。结果 粪性结肠梗阻22例，6例分别以肠梗阻、结肠占位病变行手术治疗，16例行保守治疗，均痊愈。粪性结肠穿孔6例，分别以结肠恶性肿瘤穿孔、肠绞窄行手术治疗，穿孔部位多见于直-乙状结肠交界处，2例因感染性休克、多器官功能衰竭死亡。结论 粪性结肠梗阻患者经保守治疗多能缓解症状。粪性结肠穿孔比较罕见，缺乏特异性临床表现，误诊率和病死率高，应积极行手术治疗，切除病变肠段、行Hartmann造瘘术为首选。     

肠道寄生虫感染与黏膜局部的抗感染免疫

肠道是许多病原体入侵的门户，宿主对入侵肠道的病原体可产生不同程度的抵抗力，表现为肠道黏膜的屏障作用和肠黏膜细胞、黏膜相关淋巴组织产生的一系列特异性和非特异性免疫反应等。寄生虫是单细胞或多细胞病原生物，其抗原成分相当复杂，因此，寄生虫抗原诱发的免疫应答大都是由多种免疫细胞和免疫因子参与的复杂过程。该文就肠道寄生虫与宿主肠黏膜细胞之间的相互作用和宿主肠道黏膜局部抗寄生虫感染的非特异性免疫和特异性免疫机制等进行综述。