粪菌移植治疗炎症性肠病的临床荟萃分析

发布时间：2018-11-27 13:59

【摘要】：背景和目的:炎症性肠病(inflammatory bowel disease,IBD)为病因不明的肠道慢性炎症性疾病,包括克罗恩病(crohn’s disease,CD)和溃疡性结肠炎(ulcerative colitis,UC)。目前,IBD发病机制尚未完全明确,遗传、环境、感染以及异常免疫等因素在其发生发展中发挥重要作用。并且,IBD患者肠道菌群存在异常,异常的肠道菌群可能通过诱导异常肠粘膜免疫反应、增高肠道通透性等途径,引起肠粘膜免疫失衡,诱发肠粘膜损伤,导致IBD发病。粪菌移植(fecal microbiota transplantation,FMT),即把处理后的健康人粪液移植到患者胃肠道内,建立新的肠道菌群。新近研究发现,FMT能通过调节肠道菌群及肠道免疫功能,治疗肠道感染性疾病,包括艰难梭菌性肠炎等。并且,目前已有FMT治疗IBD的实验及临床研究。为探讨FMT治疗IBD的临床效果,我们进行了该荟萃分析。方法:检索PubMed、EMBASE和中国生物医学文献数据库等,检索时限为建库至今。收集FMT治疗IBD的随机对照实验、非随机实验性研究,按照纳入标准与排除标准筛选文献,主要结果为临床缓解,次要结果为临床有效,同时观察不良反应发生率及其他相关结果,分别用用Review Manager 5.2和StatsDirect 3软件进行Meta分析。结果:纳入19篇文献,474例患者,包括随机对照实验3篇,非随机实验性研究16篇,其中队列研究1篇。Meta分析显示:对照研究中FMT组有效例数62例,对照组有效44例,p=0.008;对照研究中FMT组缓解例数40例,对照组有效21例,p=0.004;对照研究严重不良反应5例,对照组3例,p=0.50,16项研究中粪菌移植总有效率57%(95%CI=[0.39,0.74]),总缓解率28%(95%CI=[0.12,0.46]),CD患者有效率78%(95%CI=[0.53,0.95]),缓解率51%(95%CI=[0.27,0.75]),UC患者有效率53%(95%CI=[0.33,0.73]),缓解率19%(95%CI=[0.07,0.34]),严重不良反应发生率3%(95%CI=[0.01,0.07]),分析发现FMT治疗对UC的治疗缓解率及有效率高于对照组,严重不良反应两者无明显差异,其余研究发现粪菌移植对UC和CD得治疗都有效,严重不良反应少见,临床上不良反应主要为发热、腹胀、腹鸣、腹痛、腹泻等,轻微且自限。结论:FMT治疗IBD有一定的临床价值,严重不良反应相对少见,轻微的不良反应多可自行缓解,进一步的随机对照实验进行验证是必需的,关于FMT的标准化治疗及相关伦理问题也是临床工作中需要进一步解决的。
[Abstract]:Background & AIM: inflammatory bowel disease (inflammatory bowel disease,IBD) is a chronic inflammatory bowel disease with unknown etiology, including Crohn's disease (crohn's disease,CD) and ulcerative colitis (ulcerative colitis,UC). At present, the pathogenesis of IBD is not completely clear, genetic, environmental, infection and abnormal immune factors play an important role in its occurrence and development. The abnormal intestinal flora may induce abnormal intestinal mucosal immune response, increase intestinal permeability and induce intestinal mucosal immune imbalance, induce intestinal mucosal injury, and lead to the pathogenesis of IBD. Fecal bacteria transplantation (fecal microbiota transplantation,FMT), namely, the feces of treated healthy people were transplanted into the gastrointestinal tract of patients, and a new intestinal flora was established. Recent studies have found that FMT can treat intestinal infectious diseases, including Clostridium difficulty enteritis, by regulating intestinal flora and intestinal immune function. In addition, there have been experimental and clinical studies on the treatment of IBD by FMT. To investigate the clinical efficacy of FMT in the treatment of IBD, we performed this meta-analysis. Methods: PubMed,EMBASE and Chinese biomedical literature database were searched. A randomized controlled trial of FMT for the treatment of IBD was collected. The non-randomized experimental study was used to screen the literature according to the inclusion criteria and exclusion criteria. The main results were clinical remission, and the secondary results were clinical efficacy. At the same time, the incidence of adverse reactions and other related results were observed. Meta analysis was performed with Review Manager 5.2 and StatsDirect 3 respectively. Results: 474 patients were included in 19 articles, including 3 randomized controlled trials and 16 non-randomized experimental studies, including 1 cohort study. Meta analysis showed that there were 62 effective cases in FMT group and 44 cases in control group. P0. 008; There were 40 cases of remission in the FMT group, 21 cases in the control group, and p0.004 in the control group. The total effective rate of fecal bacteria transplantation was 57% (95 CI = 0.39 0.74) and the total remission rate was 28% (95CI = [0.120.46]). The effective rate of CD patients was 78% (95 CI = 0.53%), the remission rate was 51% (95 CI = 0.270.75), the effective rate of), UC patients was 53% (95 CI = 0.33 0. 73). The remission rate was 19% (95 CI = [0.07 卤0.34]), and the incidence of severe adverse reactions was 3% (95 CI = [0.01-0.07]). It was found that the remission rate and the effective rate of FMT treatment for UC were higher than those in the control group. There was no significant difference in severe adverse reactions between the two groups. Other studies showed that fecal bacteria transplantation was effective in the treatment of UC and CD, and severe adverse reactions were rare. The main adverse reactions were fever, abdominal distension, abdominal pain, diarrhea and so on, which were mild and self-limiting. Conclusion: FMT has some clinical value in the treatment of IBD, severe adverse reactions are relatively rare, and mild adverse reactions can be alleviated by themselves. Further randomized controlled trials are necessary. The standardized treatment of FMT and related ethical issues also need to be further resolved in clinical work.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R574

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