Temporal Bacterial Community Dynamics Vary Among Ulcerative Colitis Patients After Fecal Microbiota Transplantation

Temporal Bacterial Community Dynamics Vary Among Ulcerative Colitis Patients After Fecal Microbiota Transplantation
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DOI:
10.1038/ajg.2013.257
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发表时间:
2013-10-01
影响因子:
9.8
通讯作者:
Erry, David B.
Erry, David B.
中科院分区:
医学1区
文献类型:
--
作者:
Angelberger, Sieglinde;Reinisch, Walter;Erry, David B.

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目的:来自健康供体的粪便微生物群移植(FMT)是治疗艰难梭菌相关疾病的一种有效替代方法,目前正被考虑用于多种疾病,如炎症性肠病、肠易激综合征和代谢综合征。FMT后疾病的缓解被认为是通过健康供体微生物群的有效定植而促进的,但缺乏对FMT后患者微生物群组成和时间稳定性的了解。 方法:5名患有中度至重度活动性溃疡性结肠炎(梅奥评分≥6)且对标准治疗耐药的患者通过鼻空肠管和灌肠接受FMT。除了临床活动和不良事件外,使用16S rRNA基因靶向焦磷酸测序在多个时间点对患者的粪便细菌群落进行长达12周的监测。 结果:FMT引发发热和C反应蛋白暂时升高。供体的大量细菌在受体中定植,但供体微生物群定植的效率和稳定性差异很大。1名患者在12周后观察到积极的临床反应,其微生物群通过FMT得到了有效增强。这种增强的标志是供体来源的系统型相继定植,包括具有抗炎作用和/或产生短链脂肪酸的普拉梭菌、粪便罗斯氏菌和卵形拟杆菌。疾病严重程度(通过梅奥评分衡量)与肠杆菌科的过度表达和毛螺菌科的表达不足有关。 结论:本研究强调了表征随时间变化的微生物群动态对于更好地理解FMT疗效的价值,并为监测FMT在溃疡性结肠炎治疗中的成功提供了潜在有用的诊断指标。
OBJECTIVES: Fecal microbiota transplantation (FMT) from healthy donors, which is an effective alternative for treatment of Clostridium difficile-associated disease, is being considered for several disorders such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome. Disease remission upon FMT is thought to be facilitated by an efficient colonization of healthy donor microbiota, but knowledge of the composition and temporal stability of patient microbiota after FMT is lacking.METHODS: Five patients with moderately to severely active ulcerative colitis (Mayo score >= 6) and refractory to standard therapy received FMT via nasojejunal tube and enema. In addition to clinical activity and adverse events, the patients' fecal bacterial communities were monitored at multiple time points for up to 12 weeks using 16S rRNA gene-targeted pyrosequencing.RESULTS: FMT elicited fever and a temporary increase of C-reactive protein. Abundant bacteria from donors established in recipients, but the efficiency and stability of donor microbiota colonization varied greatly. A positive clinical response was observed after 12 weeks in one patient whose microbiota had been effectively augmented by FMT. This augmentation was marked by successive colonization of donor-derived phylotypes including the anti-inflammatory and/or short-chain fatty acid-producing Faecalibacterium prausnitzii, Rosebura faecis, and Bacteroides ovatus. Disease severity (as measured by the Mayo score) was associated with an overrepresentation of Enterobacteriaceae and an underrepresentation of Lachnospiraceae.CONCLUSIONS: This study highlights the value of characterizing temporally resolved microbiota dynamics for a better understanding of FMT efficacy and provides potentially useful diagnostic indicators for monitoring FMT success in the treatment of ulcerative colitis.