粪菌移植治疗炎症性肠病的临床有效性及安全性研究

发布时间：2018-03-30 15:31

本文选题：克罗恩病　切入点：粪菌移植　出处：《南京医科大学》2017年博士论文

【摘要】：背景及目的:肠道菌群在肠道疾病的发生发展中发挥重要作用。遗传、环境、饮食和抗生素等多种因素使炎症性肠病(Inflammatory bowel disease,IBD)患者肠道菌群失调,表现为拟杆菌门和厚壁菌门比例失调、变形菌门增加或出现不常见细菌。粪菌移植(Fecal microbiota transplantation,FMT)作为肠道菌群重建的手段,被认为对难治性炎症性肠病具有挽救治疗价值。本研究拟探讨经中消化道单次粪菌移植治疗难治性克罗恩病(Crohn's disease,CD)的安全性、可行性及有疗效性。方法:本研究建立了标准化的粪菌移植实验室及临床流程。所纳入研究对象为Harvey-Bradshaw Index(HBI)评分≥7,且对常规治疗无效的克罗恩病患者。受试者治疗前一周停止所有针对克罗恩病的药物治疗。经中消化道接受单次FMT,并分别在治疗前3天、治疗后3天、治疗后1周、1月、3月、6月、9月、12月、15月进行随访,分别从临床症状、实验室检查指标等评估FMT的有效率、缓解率,及不良事件的发生率。所有患者满足最短随访时间为治疗后6个月。结果:16sRNA测序显示经纯化后的粪便菌群组成结构与粪便原始菌种无显著性差别。标准化的粪菌制备和临床流程使FMT更易于操作。FMT治疗后最长随访15个月,治疗后1个月的临床有效率及缓解率分别为86.7%(26/30)和76.7%(23/30),高于其它随访点。患者体重、血脂水平均较治疗前显著改善。此外,FMT还快速诱导并维持克罗恩病相关的腹痛缓解。在长达15个月的随访期,未发生与FMT相关的严重不良反应。结论:这是一项FMT治疗难治性CD的前瞻性研究。本研究结果显示经中消化道单次FMT是一项安全、可行、有效的CD挽救治疗方案。目的及背景:激素依赖型溃疡性结肠炎(Ulcerative colitis,UC)的治疗是临床面临的一种挑战,粪菌移植(Fecal microbiota transplantation,FMT)作为肠道菌群重建的重要手段,对激素依赖型UC的临床疗效尚不明确。本研究基于临床实践设计了 FMT升阶治疗策略,并观察其对激素依赖型UC的临床疗效及安全性。方法:本研究共纳入15例激素依赖型溃疡性结肠炎患者,通过进行FMT升阶治疗,临床随访3个月以上,观察其临床疗效及安全性,并通过16sRNA测序检测患者治疗前、治疗后及相应供体的肠道菌群结构,分析其菌群变化与供体的相关性。结果:15例患者中,一例失访。57%(8/14)的患者经过FMT升阶治疗达到临床改善,并顺利脱离激素依赖。8例临床治疗有效的患者中,5例仅接受一次FMT治疗,1例接受两次FMT,2例接受两次FMT加一个疗程的激素治疗。4例患者达临床缓解,并在整个随访期维持(3-18个月)。6例患者未达临床改善标准,并未脱离激素依赖,其中有3例在FMT治疗后有短暂改善,但很快复发。16sRNA测序显示,FMT治疗有效的UC患者,其肠道菌群结构治疗后显著改变,并向供体菌群结构接近。在整个治疗和随访过程中,未发生与FMT相关的严重不良事件。结论:粪菌移植升阶治疗策略显示了其对激素依赖型UC的临床治疗价值,并且其疗效可能与肠道菌群重建密切相关。
[Abstract]:Background and purpose: intestinal microflora in the occurrence and development of intestinal diseases play an important role in the environment, a variety of factors. Genetic, diet and antibiotics to inflammatory bowel disease (Inflammatory bowel, disease, IBD) imbalance of intestinal flora, manifested as Bacteroidetes and Firmicutes than patients with disorders, Proteobacteria or increase no common bacteria. Fecal bacteria transplantation (Fecal microbiota transplantation, FMT) as a means of intestinal flora reconstruction, is believed to have saved value for treatment of refractory inflammatory bowel disease. This study aims to investigate the digestive tract in a single fecal bacteria transplantation in the treatment of refractory Crohn's disease (Crohn's disease CD) security there is, feasibility and efficacy. Methods: This study established and clinical process of FMT laboratory standards. The objects included in the study for Harvey-Bradshaw Index (HBI) score less than 7, and respond to conventional therapy of Crohn's disease Patients. Subjects a week before treatment all drugs for the treatment of Crohn's disease in the digestive tract. The stop received a single FMT, and respectively before treatment, 3 days, 3 days after treatment, 1 weeks after treatment, January, March, June, September, December, were followed up for 15 months, respectively, from the clinical symptoms and the laboratory examination indexes to assess FMT efficiency, response rate, and incidence of adverse events. All patients meet the shortest follow-up time was 6 months after treatment. Results: 16sRNA sequencing showed that the purified fecal flora composition and fecal original strain had no significant difference. The standard of fecal bacteria the preparation and clinical process to make FMT easier to operate after.FMT treatment, the longest follow-up period of 15 months, 1 months after treatment, clinical effective rate and remission rate was 86.7% (26/30) and 76.7% (23/30), higher than that of the other follow-up. Patients with body weight, blood lipid level was significantly improved compared with before treatment. In addition, FMT also induced rapid Abdominal pain related Crohn's disease and maintain remission. During a follow-up period of 15 months, no serious adverse reaction associated with FMT. Conclusion: This is a prospective study of FMT in the treatment of refractory CD. The results of this study showed that the digestive tract in a single FMT is a safe, feasible, have the effect of CD rescue treatment. Objective and background: steroid dependent ulcerative colitis (Ulcerative colitis, UC) treatment is a clinical problem, fecal bacteria transplantation (Fecal microbiota transplantation, FMT) as an important means of intestinal flora reconstruction, clinical effect of hormone dependent UC is not clear based on clinical practice. This study designed FMT L-order treatment strategy, and to observe the clinical efficacy and safety of hormone dependent UC. Methods: This study included 15 cases of patients with steroid dependent ulcerative colitis, L-order treatment by FMT with clinical Visit for more than 3 months, to observe the clinical efficacy and safety, and through 16sRNA sequencing to detect the patients before treatment, after treatment and corresponding donor intestinal flora and its correlation analysis of microflora and donor. Results: in 15 cases, one cases lost.57% (8/14) patients after FMT L-order treatment to clinical improvement, and smooth out of hormone dependent clinical.8 cases patients, 5 cases received only a FMT treatment, 1 patients received two times of FMT, 2 cases received hormone therapy two times a course of FMT plus.4 patients reached clinical remission, and maintained throughout the follow-up period (3-18 months).6 patients did not reach the standard of clinical improvement, not from hormone dependent, of which 3 cases had transient improvement in FMT after treatment, but soon relapsed.16sRNA sequencing revealed that FMT is effective in the treatment of UC patients, a significant change in the structure of intestinal flora after treatment, and close to the donor group in structure. No serious adverse events related to FMT were observed during the whole treatment and follow-up. Conclusion: the advanced treatment strategy of fecal bacteria shows its clinical value for hormone dependent UC, and its efficacy may be closely related to intestinal microflora reconstruction.

【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R574

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