Alteration of Intestinal Dysbiosis by Fecal Microbiota Transplantation Does not Induce Remission in Patients with Chronic Active Ulcerative Colitis
Alteration of Intestinal Dysbiosis by Fecal Microbiota Transplantation Does not Induce Remission in Patients with Chronic Active Ulcerative Colitis
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DOI：
10.1097/mib.0b013e31829ea325
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发表时间：
2013-09-01
影响因子：
4.9
通讯作者：
Hoegenauer, Christoph
中科院分区：
文献类型：
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作者：
Kump, Patrizia K.;Groechenig, Hans-Peter;Hoegenauer, Christoph
背景：在溃疡性结肠炎(UC)患者中，肠道微生物区系的改变，称为生物失调，被认为是导致肠道炎症的因素。粪便微生物区系移植(FMT)是治疗难辨梭状芽胞杆菌结肠炎复发的有效方法，也是由生物失调引起的。本研究的目的是探讨FMT对UC患者是否有益，以及是否可以逆转UC的生态失调。方法：对6例对标准药物治疗无效的慢性活动期UC患者采用结肠镜下给予FMT治疗。使用高通量焦磷酸测序技术，通过基于16S rDNA的微生物群落分析，评估结肠微生物区系的变化。结果：所有患者在FMT后的前2周内都经历了短期的临床改善。然而，没有一例患者获得临床缓解。微生物区系分析显示，FMT后不同患者之间肠道微生物区系的改变存在差异。在3名患者中，结肠微生物区系向供体微生物区系转变；然而，这与临床反应无关。在菌门水平上，FMT后变形杆菌显著减少，类杆菌显著增加。结论：在慢性主动治疗难治性UC中，单一结肠镜供体粪便FMT不能有效地诱导缓解。肠道微生物区系的组成发生了显著的变化，导致UC相关的微生物失调得到了部分改善。这些结果表明，UC的生物失调至少部分是由炎症和腹泻引起的继发性现象，而不是这种疾病中炎症的原因。
Background:In patients with ulcerative colitis (UC), alterations of the intestinal microbiota, termed dysbiosis, have been postulated to contribute to intestinal inflammation. Fecal microbiota transplantation (FMT) has been used as effective therapy for recurrent Clostridium difficile colitis also caused by dysbiosis. The aims of the present study were to investigate if patients with UC benefit from FMT and if dysbiosis can be reversed.Methods:Six patients with chronic active UC nonresponsive to standard medical therapy were treated with FMT by colonoscopic administration. Changes in the colonic microbiota were assessed by 16S rDNA-based microbial community profiling using high-throughput pyrosequencing from mucosal and stool samples.Results:All patients experienced short-term clinical improvement within the first 2 weeks after FMT. However, none of the patients achieved clinical remission. Microbiota profiling showed differences in the modification of the intestinal microbiota between individual patients after FMT. In 3 patients, the colonic microbiota changed toward the donor microbiota; however, this did not correlate with clinical response. On phylum level, there was a significant reduction of Proteobacteria and an increase in Bacteroidetes after FMT.Conclusions:FMT by a single colonoscopic donor stool application is not effective in inducing remission in chronic active therapy-refractory UC. Changes in the composition of the intestinal microbiota were significant and resulted in a partial improvement of UC-associated dysbiosis. The results suggest that dysbiosis in UC is at least in part a secondary phenomenon induced by inflammation and diarrhea rather than being causative for inflammation in this disease.