Prospects of Fecal Microbiota Transplantation for Inflammatory Bowel Disease in the Context of Biological Agents
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摘要: 炎症性肠病（inflammatory bowel disease，IBD）是一种慢性非特异性肠道炎症性疾病，目前发病机制尚不清楚，缺乏有效的治疗手段。生物制剂的问世，为IBD的治疗开启了新的篇章，一部分患者能达到临床缓解甚至黏膜愈合，但在临床实践中，仍然有不少患者初始治疗无应答或继发性失应答，不能完全控制疾病的进展。研究显示，肠道微生物群的改变在IBD发生发展中发挥关键作用，且可能作为评估生物制剂疗效的预测因子。粪菌移植（fecal microbiota transplantation，FMT）作为一种重建患者肠道微生态的新型治疗手段，在改善IBD症状、诱导并维持疾病的黏膜愈合甚至组织学缓解方面具有一定疗效。在生物制剂时代，FMT在IBD患者中的应用前景如何呢，将总结国内外相关的研究成果，为FMT在生物制剂时代治疗IBD的潜力、可行性等提供理论依据。Abstract: Inflammatory bowel disease （IBD） is a chronic, non-specific inflammatory condition of the intestines, and its mechanisms are still unclear, with effective treatments lacking. The advent of biologics has opened a new chapter in the treatment of IBD, with some patients achieving clinical remission or even mucosal healing. However, in clinical practice, there are still quite a few patients who either do not respond to initial treatment or experience secondary loss of response, making it difficult to fully control disease progression. Research shows that changes in the gut microbiota play a crucial role in the onset and progression of IBD, and they may serve as predictive factors for assessing the efficacy of biologics. Fecal microbiota transplantation （FMT）, as a new treatment method to restore the gut microecology of patients, has shown some effectiveness in improving IBD symptoms, inducing and maintaining mucosal healing, and even achieving histological remission. What does the future hold for the application of FMT in IBD patients in the era of biologics? This review will summarize relevant research results from both domestic and international sources to provide a theoretical basis for the potential and feasibility of using FMT in treating IBD during the biologics era.
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表 1 FMT治疗IBD的安全性及有效性
Table 1. Safety and efficacy of FMT in treatingt IBD
作者 研究类型 纳入人群及特征 有效性 安全性 Zhang等[27] 病例报告 （1）34岁男性，重度CD，有结肠瘘，14 cm×8 cm×10 cm腹腔炎性包块；（2）FMT作为挽救治疗。 （1）FMT后1周，患者的发热、粘液脓血便、腹痛等症状明显减轻，腹腔内炎性包块大小较FMT前明显缩小；（2）FMT后3个月炎性包块吸收，内瘘改善。 未发生FMT不良事件 Vandenplas Y等[28] 病例报告 （1）4个月大婴儿，重度UC，对硫唑嘌呤、皮质类固醇、益生菌、IFX单抗治疗均无效；（2）连续7次FMT作为挽救治疗。 最后一次进行FMT后6个月，继续停止所有药物近3个月后组织学显示正常。 有出汗、呕吐、脸色苍白、心动过速（血压保持在正常水平）、发热，但在一个小时内自然恢复。 Shimizu H
等[29]病例报告 （1）11岁女性患者，有皮质类固醇依赖性UC；（2）对5-ASA、IFX、他克莫司治疗均无反应。 在FMT后40周仍处于临床缓解 未报告不良事件 Wang等[30] 病例报告 2例对激素及TNF-α抗体治疗均无效的难治性免疫相关肠炎患者； 所有患者在FMT后均获得症状缓解及镜下黏膜愈合 未报告不良事件 Uygun A
等[31]前瞻性非对照研究 （1）30例UC患者，所有患者在入组前均使用了标准的类固醇、硫唑嘌呤和抗肿瘤坏死因子治疗，但均无效；（2）除5-ASA外，所有药物在FMT前4周停止使用。 30例患者中有21例（70%）出现了临床反应；30例患者中有13例（43.3%）在第12周获得了临床和内镜下缓解 7例（23.3%）患者出现恶心、呕吐、腹痛、腹泻等轻度不良反应，在对症治疗后1天内消失。 Neeraj等[32] Meta分析 （1）4项前瞻性随机对照设计研究，共277例UC患者；
（2）均为经传统药物和免疫抑制剂治疗失败的UC患者。（1）与安慰剂组（自体粪便或生理盐水，22.6%）相比，FMT组内镜下缓解率更高（42.1%）；（2）5例肠皮瘘CD患者中80%（4/5）在FMT后出现肠皮瘘管闭合； 未报告不良事件 He Z等[33] 前瞻性非对照研究 25例合并腹腔内炎症性肿块的CD
患者。首次FMT后3个月，分别有68%（17/25）和52.0%（13/25）的患者达到临床缓解。 未报告不良事件 Xiang L
等[34]前瞻性非对照研究 174例CD患者。 75.3%（131/174）的患者在FMT后1个月达到临床缓解； 未报告不良事件 Costello
等[35]前瞻性对照研究 混合供者FMT（n=38）或自体FMT（n=35） （1）接受混合供者FMT的UC患者32%（12/38），自体FMT的UC患者9%达到（9/35）达到无激素缓解。（2）接受混合供者FMT并在第8周时达到缓解的12例UC中，42%（5/12）在12个月时仍维持临床缓解； 混合供者FMT组中有3例不良事件（2肺炎，艰难梭菌感染、疾病加重）；自体FMT组中有2例（贫血，转氨酶升高）。 Wu X等[36] 前瞻性试验的回顾性分析 44例活动性UC患者 FMT后3个月，分别有50.0%（22/44）和29.5%（13/44）的患者获得临床缓解； 大多数不良反应：排便频率增加、发热、腹痛和皮肤瘙痒都是短暂的，无需医疗干预即可缓解 Paramsothy S等[22] 双盲、随机、安慰剂对照试验 85例UC患者，42例随机分配到FMT组（多供体），43例分配到安慰剂组
（等渗盐水）以Mayo评分评价疗效，FMT组患者（17/42，41%）疗效显著高于安慰剂组（5/43，12%）。 实验组1例难治性UC患者发生疾病恶化，另一例因FMT导致身体不适而退出。 
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