Predicting recurrence of Clostridium difficile infection following encapsulated fecal microbiota transplantation.
Predicting recurrence of Clostridium difficile infection following encapsulated fecal microbiota transplantation.
复制标题
DOI：
10.1186/s40168-018-0549-6
复制
发表时间：
2018-09-18
期刊：
影响因子：
15.5
通讯作者：
Sadowsky MJ
中科院分区：
文献类型：
--
作者：
Staley C;Kaiser T;Vaughn BP;Graiziger CT;Hamilton MJ;Rehman TU;Song K;Khoruts A;Sadowsky MJ
粪便微生物群移植（FMT）是治疗复发性艰难梭菌感染（rCDI）的有效方法。使用冻干、封装的FMT供体材料（cap-FMT）可提供简单的给药途径，并在大多数rCDI患者中保持临床有效性。我们假设微生物群对cap-FMT的反应的特定变化可以预测临床结果。我们进一步评估了供体微生物群植入的程度，以确定供体转移对恢复的贡献程度。总共有89名患者接受了100次单独的cap-FMT治疗，成功率（cap-FMT后60天无rCDI）为80%。在应答者中，在患者的FMT前样品中观察到的较低α多样性（ANOVA P < 0.05）在cap-FMT后恢复。在FMT后1周，群落组成因临床结果而异（ANOSIM P < 0.001），在应答者和供体样品中，各家族（毛螺菌科、瘤胃球菌科和拟杆菌科）之间的丰度相似。从cap-FMT后7天收集的样品中显示出不同丰度的结果（响应与复发）的家庭用于构建基于回归树的模型来预测复发。结果显示，预测复发的训练准确率为100%，并且该模型对cap-FMT后8-20天收集的样本的测试数据集的准确率为97%。使用贝叶斯算法SourceTracker对植入程度的评估显示，大约50%的FMT后应答者群落可归因于供体微生物群，而另外20-30%的群落与由所有供体样品组成的复合健康微生物群相似。基于回归树的微生物群落分析确定了与7天后的临床反应显著相关的分类群，这可以有针对性地改善微生物治疗。此外，cap-FMT后健康组合的恢复仅部分归因于明确的供体植入，并继续向整体健康组合发展，独立于供体。本文的在线版本（10.1186/s40168-018-0549-6）包含补充材料，可供授权用户使用。
Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The use of freeze-dried, encapsulated donor material for FMT (cap-FMT) allows for an easy route of administration and remains clinically effective in the majority of rCDI patients. We hypothesized that specific shifts in the microbiota in response to cap-FMT could predict clinical outcome. We further evaluated the degree of donor microbiota engraftment to determine the extent that donor transfer contributed to recovery. In total, 89 patients were treated with 100 separate cap-FMTs, with a success rate (no rCDI 60 days post cap-FMT) of 80%. Among responders, the lower alpha diversity (ANOVA P < 0.05) observed among patient’s pre-FMT samples was restored following cap-FMT. At 1 week post-FMT, community composition varied by clinical outcome (ANOSIM P < 0.001), with similar abundances among families (Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae) in responder and donor samples. Families that showed differential abundances by outcome (response vs. recurrence) from samples collected 7 days following cap-FMT were used to construct a regression tree-based model to predict recurrence. Results showed a training accuracy of 100% to predict recurrence and the model was 97% accurate against a test data set of samples collected 8–20 days following cap-FMT. Evaluation of the extent of engraftment using the Bayesian algorithm SourceTracker revealed that approximately 50% of the post-FMT communities of responders were attributable to donor microbiota, while an additional 20–30% of the communities were similar to a composite healthy microbiota consisting of all donor samples. Regression tree-based analyses of microbial communities identified taxa significantly related to clinical response after 7 days, which can be targeted to improve microbial therapeutics. Furthermore, reinstatement of a healthy assemblage following cap-FMT was only partially attributable to explicit donor engraftment and continued to develop towards an overall healthy assemblage, independent of donor. The online version of this article (10.1186/s40168-018-0549-6) contains supplementary material, which is available to authorized users.
登录
查看更多内容
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：
3.7
作者：
Giel JL;Sorg JA;Sonenshein AL;Zhu J
通讯作者：
Zhu J
影响因子：
56.9
作者：
Li, Simone S.;Zhu, Ana;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
4.8
作者：
Clark, JS
通讯作者：
Clark, JS
影响因子：
11.8
作者：
McDonald, L. Clifford;Gerding, Dale N.;Wilcox, Mark H.
通讯作者：
Wilcox, Mark H.