Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease.
Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease.
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DOI：
10.1097/mib.0000000000000893
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发表时间：
2016-09
影响因子：
4.9
通讯作者：
Moss AC
中科院分区：
文献类型：
--
作者：
Vaughn BP;Vatanen T;Allegretti JR;Bai A;Xavier RJ;Korzenik J;Gevers D;Ting A;Robson SC;Moss AC
克罗恩病（CD）患者管腔中的微生物群的特征是多样性降低，特别是厚壁菌门和拟杆菌门。目前尚不清楚从健康个体引入肠道微生物群是否可以纠正这种生态失调并逆转粘膜炎症。我们研究了从健康个体到活动性CD受试者对粪便微生物移植（FMT）的反应。我们进行了从健康供体到活动性CD受试者的FMT的前瞻性开放标签研究（非对照）。通过结肠镜检查进行单次FMT。接受者的微生物多样性，粘膜T细胞表型和临床和炎症参数在12周内进行了测量，安全性超过26周。19例受试者接受了FMT治疗并完成了研究随访。58%（11/19）的患者在FMT后表现出临床反应（HBI降低> 3）。15例受试者有足够的分析前/后粪便样本。FMT后微生物多样性显著增加（p=0.02）。这在临床应答者中比无应答者更大。在4周时，通过Bray-Curtis指数评估，出现临床应答的患者表现出粪便微生物组成向其供体特征的显著变化（p=0.003）。FMT后，在受体的固有层中也注意到调节性T细胞（CD 4 + CD 25 + CD 127 lo）的增加。在26周的研究期间没有发现严重的不良事件。在这项开放标签研究中，FMT导致活动性CD患者的微生物细菌多样性扩大。FMT总体上是安全的，尽管临床反应是可变的。在进行FMT治疗CD的随机临床试验之前，需要确定影响临床反应的供体微生物因素。临床试验ID #NCT 01847170
The microbiota in the lumen of patients with Crohn’s disease (CD) is characterized by reduced diversity, particularly Firmicutes and Bacteroidetes. It is unknown whether the introduction of the intestinal microbiota from healthy individuals could correct this dysbiosis and reverse mucosal inflammation. We investigated the response to fecal microbial transplantation (FMT) from healthy individuals to subjects with active CD We performed a prospective open-label study (uncontrolled) of FMT from healthy donors to subjects with active CD. A single FMT was performed via colonoscopy. Recipients’ microbial diversity, mucosal T-cell phenotypes and clinical and inflammatory parameters were measured over 12 weeks, and safety over 26 weeks. Nineteen subjects were treated with FMT and completed the study follow-up. Fifty-eight percent (11/19) demonstrated a clinical response (HBI decrease > 3) following FMT. Fifteen subjects had sufficient pre/post fecal samples for analysis. A significant increase in microbial diversity occurred after FMT (p=0.02). This was greater in clinical responders than non-responders. Patients who experienced a clinical response demonstrated a significant shift in fecal microbial composition towards their donor’s profile as assessed by the Bray-Curtis index at 4 weeks (p=0.003). An increase in regulatory T-cells (CD4+CD25+CD127lo) was also noted in recipients’ lamina propria following FMT. No serious adverse events were noted over the 26-week study period. In this open label study, FMT led to an expansion in microbial bacterial diversity in patients with active CD. FMT was overall safe, although the clinical response was variable. Determining donor microbial factors that influence clinical response is needed prior to randomized clinical trials of FMT in CD. ClinicalTrials ID # NCT01847170