The GRAFT study: Gut RecolonizAtion by Fecal Transplantation

摘要 艰难梭菌是最常见的细菌性腹泻的原因。那些 以前的C。艰难梭菌感染（CDI）的患者复发感染的风险很高。复发性CDI 通常发生在正常的肠道微生物群被破坏时。肠道微生物群失调 易患CDI，尽管治疗，仍有30%的患者会复发。一种新颖的方式来 预防CDI复发的方法是将健康个体的粪便滴入患者的肠道， CDI患者，从而恢复肠道微生物群的平衡。然而，目前尚不清楚是否或 非粪便微生物群移植（FMT）是预防CDI复发的有效选择 当与抗生素同时使用时。我们提出了一个试验性随机双盲安慰剂- 一项在有CDI病史的患者中比较口服FMT与安慰剂的对照试验，目前 正在接受抗生素治疗我们将在给药前、给药期间和给药后收集受试者的粪便样本。 在FMT之后，收集关于微生物群组成的宏基因组学和微生物学数据， 函数和CDI递归。该试验的主要结果是肠道微生物组成， 功能次要结局是可行性和安全性，以及试验期间复发的CDI 期在这项3组研究中，FMT将每日通过口服胶囊给药， 第1组中来自通用供体的粪便微生物群，在抗生素治疗结束时施用 组2和组3将接受安慰剂。这项研究的结果将提供必要的 试验数据，以检查是否在接受抗生素治疗的患者中同时进行FMT 复发性CDI的高风险可以维持多样化的健康GI微生物群。如果发现有效， 一项评价FMT和抗生素同时治疗预防 住院患者中的复发性CDI将是必要的。

Abstract Clostridium difficile is the most frequent bacterial cause of antibiotic-associated diarrhea. Those with a previous C. difficile infection (CDI) are at high risk of recurrent infection. Recurrent CDI often occurs when the normal gut microbiota are disrupted. Dysbiosis of the gut microbiota predisposes to CDI which, despite treatment can recur in 30% of patients. A novel way to prevent CDI recurrence is by instilling feces from a healthy individual into the intestine of the CDI patient, thereby restoring balance in the gut microbiota. However, it is unknown whether or not fecal microbiota transplantation (FMT) is an efficacious choice for CDI recurrence prevention when used concurrently with antibiotics. We propose a pilot randomized, double-blind placebo- controlled trial comparing oral FMT with placebo in patients with a history of CDI, currently undergoing antibiotic treatment. We will collect fecal samples from subjects prior to, during, and after FMT and collect metagenomics and microbiologic data on microbiota composition and function, and CDI recurrence. The trial's primary outcome is gut microbial composition and function. Secondary outcomes are feasibility and safety, and recurrent CDI during the trial period. In this 3 group study, FMT will be administered daily via oral capsules containing frozen fecal microbiota from universal donors in group 1, administered at the end of antibiotic treatment for group 2 and group 3 will receive placebo. The results of this study will provide the necessary pilot data to examine whether or not concurrent FMT in antibiotic treated patients who are at high risk for recurrent CDI can maintain a diverse healthy GI microbiota. If found to be effective, a trial evaluating the effect of concurrent FMT and antibiotic treatment for prevention of recurrent CDI in hospitalized patients would be warranted.