發(fā)布時(shí)間：2018-03-30 15:31

  本文選題：克羅恩病　切入點(diǎn)：糞菌移植　出處：《南京醫(yī)科大學(xué)》2017年博士論文

【摘要】：背景及目的:腸道菌群在腸道疾病的發(fā)生發(fā)展中發(fā)揮重要作用。遺傳、環(huán)境、飲食和抗生素等多種因素使炎癥性腸病(Inflammatory bowel disease,IBD)患者腸道菌群失調(diào),表現(xiàn)為擬桿菌門(mén)和厚壁菌門(mén)比例失調(diào)、變形菌門(mén)增加或出現(xiàn)不常見(jiàn)細(xì)菌。糞菌移植(Fecal microbiota transplantation,FMT)作為腸道菌群重建的手段,被認(rèn)為對(duì)難治性炎癥性腸病具有挽救治療價(jià)值。本研究擬探討經(jīng)中消化道單次糞菌移植治療難治性克羅恩病(Crohn's disease,CD)的安全性、可行性及有療效性。方法:本研究建立了標(biāo)準(zhǔn)化的糞菌移植實(shí)驗(yàn)室及臨床流程。所納入研究對(duì)象為Harvey-Bradshaw Index(HBI)評(píng)分≥7,且對(duì)常規(guī)治療無(wú)效的克羅恩病患者。受試者治療前一周停止所有針對(duì)克羅恩病的藥物治療。經(jīng)中消化道接受單次FMT,并分別在治療前3天、治療后3天、治療后1周、1月、3月、6月、9月、12月、15月進(jìn)行隨訪,分別從臨床癥狀、實(shí)驗(yàn)室檢查指標(biāo)等評(píng)估FMT的有效率、緩解率,及不良事件的發(fā)生率。所有患者滿足最短隨訪時(shí)間為治療后6個(gè)月。結(jié)果:16sRNA測(cè)序顯示經(jīng)純化后的糞便菌群組成結(jié)構(gòu)與糞便原始菌種無(wú)顯著性差別。標(biāo)準(zhǔn)化的糞菌制備和臨床流程使FMT更易于操作。FMT治療后最長(zhǎng)隨訪15個(gè)月,治療后1個(gè)月的臨床有效率及緩解率分別為86.7%(26/30)和76.7%(23/30),高于其它隨訪點(diǎn)�；颊唧w重、血脂水平均較治療前顯著改善。此外,FMT還快速誘導(dǎo)并維持克羅恩病相關(guān)的腹痛緩解。在長(zhǎng)達(dá)15個(gè)月的隨訪期,未發(fā)生與FMT相關(guān)的嚴(yán)重不良反應(yīng)。結(jié)論:這是一項(xiàng)FMT治療難治性CD的前瞻性研究。本研究結(jié)果顯示經(jīng)中消化道單次FMT是一項(xiàng)安全、可行、有效的CD挽救治療方案。目的及背景:激素依賴型潰瘍性結(jié)腸炎(Ulcerative colitis,UC)的治療是臨床面臨的一種挑戰(zhàn),糞菌移植(Fecal microbiota transplantation,FMT)作為腸道菌群重建的重要手段,對(duì)激素依賴型UC的臨床療效尚不明確。本研究基于臨床實(shí)踐設(shè)計(jì)了 FMT升階治療策略,并觀察其對(duì)激素依賴型UC的臨床療效及安全性。方法:本研究共納入15例激素依賴型潰瘍性結(jié)腸炎患者,通過(guò)進(jìn)行FMT升階治療,臨床隨訪3個(gè)月以上,觀察其臨床療效及安全性,并通過(guò)16sRNA測(cè)序檢測(cè)患者治療前、治療后及相應(yīng)供體的腸道菌群結(jié)構(gòu),分析其菌群變化與供體的相關(guān)性。結(jié)果:15例患者中,一例失訪。57%(8/14)的患者經(jīng)過(guò)FMT升階治療達(dá)到臨床改善,并順利脫離激素依賴。8例臨床治療有效的患者中,5例僅接受一次FMT治療,1例接受兩次FMT,2例接受兩次FMT加一個(gè)療程的激素治療。4例患者達(dá)臨床緩解,并在整個(gè)隨訪期維持(3-18個(gè)月)。6例患者未達(dá)臨床改善標(biāo)準(zhǔn),并未脫離激素依賴,其中有3例在FMT治療后有短暫改善,但很快復(fù)發(fā)。16sRNA測(cè)序顯示,FMT治療有效的UC患者,其腸道菌群結(jié)構(gòu)治療后顯著改變,并向供體菌群結(jié)構(gòu)接近。在整個(gè)治療和隨訪過(guò)程中,未發(fā)生與FMT相關(guān)的嚴(yán)重不良事件。結(jié)論:糞菌移植升階治療策略顯示了其對(duì)激素依賴型UC的臨床治療價(jià)值,并且其療效可能與腸道菌群重建密切相關(guān)。
[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.

【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R574

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相關(guān)期刊論文 前8條

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本文編號(hào)：1686511