Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study.
Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study.
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DOI：
10.1038/ajg.2017.6
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Khoruts A
中科院分区：
文献类型：
--
作者：
Staley C;Hamilton MJ;Vaughn BP;Graiziger CT;Newman KM;Kabage AJ;Sadowsky MJ;Khoruts A
粪便微生物群移植（FMT）越来越多地用于治疗仅用抗生素无法治愈的复发性艰难梭菌感染（R-CDI）。此外，FMT正在研究各种适应症，其中肠道微生物群落的恢复或重建被假设是有益的。我们试图开发一种稳定的、冷冻干燥的标准化粪便微生物群的胶囊化制剂，其可以在临床实践和研究中轻松方便地用于FMT。我们系统地开发了一种冻干方案，该方案保留了粪便微生物群中所有分类谱中细菌的活力，并产生了能够实现一致包封的理化性质。我们还用一系列剂量的包囊微生物群治疗了一组R-CDI患者，并分析了接受者粪便微生物群的相关变化。优化的冻干制剂满足了我们对理化性质、包封容易性、在不同温度下的稳定性以及体外和体内（无菌小鼠）微生物群活力的所有预设目标。49名患者接受了胶囊治疗。总体而言，43/49（88%）例患者获得了临床成功，定义为2个月内无CDI复发。粪便微生物组分析表明，FMT治疗后1个月粪便微生物群落接近正常化。使用最低剂量（2-3粒胶囊中2.1-2.5×1011个细菌）而不使用任何结肠泻下剂的最简单方案在临床结局和微生物群植入方面表现同样良好。来自健康供体的封装的冻干粪便微生物群的单次施用在治疗难治性R-CDI综合征方面非常成功。
Fecal microbiota transplantation (FMT) is increasingly being used for treatment of recurrent Clostridium difficile infection (R-CDI) that cannot be cured with antibiotics alone. In addition, FMT is being investigated for a variety of indications where restoration or restructuring of the gut microbial community is hypothesized to be beneficial. We sought to develop a stable, freeze-dried encapsulated preparation of standardized fecal microbiota that can be used for FMT with ease and convenience in clinical practice and research. We systematically developed a lyophilization protocol that preserved the viability of bacteria across the taxonomic spectrum found in fecal microbiota and yielded physicochemical properties that enabled consistent encapsulation. We also treated a cohort of R-CDI patients with a range of doses of encapsulated microbiota and analyzed the associated changes in the fecal microbiome of the recipients. The optimized lyophilized preparation satisfied all our preset goals for physicochemical properties, encapsulation ease, stability at different temperatures, and microbiota viability in vitro and in vivo (germ-free mice). The capsule treatment was administered to 49 patients. Overall, 43/49 (88%) of patients achieved a clinical success, defined as no recurrence of CDI over 2 months. Analysis of the fecal microbiome demonstrated near normalization of the fecal microbial community by 1 month following FMT treatment. The simplest protocol using the lowest dose (2.1–2.5×1011 bacteria in 2–3 capsules) without any colon purgative performed equally well in terms of clinical outcomes and microbiota engraftment. A single administration of encapsulated, freeze-dried fecal microbiota from a healthy donor was highly successful in treating antibiotic-refractory R-CDI syndrome.
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影响因子：
15.5
作者：
Shankar V;Hamilton MJ;Khoruts A;Kilburn A;Unno T;Paliy O;Sadowsky MJ
通讯作者：
Sadowsky MJ
影响因子：
14.9
作者：
Pruesse E;Quast C;Knittel K;Fuchs BM;Ludwig W;Peplies J;Glöckner FO
通讯作者：
Glöckner FO
DOI：
10.1016/j.cgh.2016.02.018
发表时间：
2016-10
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
Khoruts A;Rank KM;Newman KM;Viskocil K;Vaughn BP;Hamilton MJ;Sadowsky MJ
通讯作者：
Sadowsky MJ
影响因子：
4.4
作者：
Schloss, Patrick D.;Westcott, Sarah L.;Weber, Carolyn F.
通讯作者：
Weber, Carolyn F.
影响因子：
14.9
作者：
Claesson MJ;Wang Q;O'Sullivan O;Greene-Diniz R;Cole JR;Ross RP;O'Toole PW
通讯作者：
O'Toole PW